表达猪链球菌2型保护性抗原重组猪痘病毒的构建、特性分析及其小鼠免疫评估
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摘要
猪链球菌2型(Streptococcus suis type2,SS2)可引起猪患脑膜炎、关节炎、心内膜炎、肺炎及败血症,同时也能感染人并导致死亡,是一种重要的人畜共患病病原体。猪痘病毒(Swinepox virus, SPV)在自然情况下只感染猪,并且症状温和,能自行康复,其作为病毒载体有很多优点,故适合用于重组疫苗的开发。本研究以SPV作为载体构建了6个表达SS2保护性抗原的重组病毒,并对重组病毒进行了免疫学评价。
1SPV的分离及猪痘的血清学调查
用PK-15细胞在猪痘发病猪的痂皮和脓疱中分离到一株SPV。对包含SPV特异性序列在内的三段核酸序列进行了扩增和测序,与SPV17077-99株相比,三段序列的核苷酸同源性分别为91%、96%和99%。此外,为了了解猪痘的流行现状,利用琼脂扩散试验对来自江西、安徽、湖北、江苏、广东及上海共1004份成年猪血清进行了猪痘血清学调查。结果表明,猪痘在猪群中较少发生,在被检测的1004份样品中只有40份阳性,阳性率仅为4%,但被调查的六个地区都有分布。
2表达lacZ基因重组猪痘病毒的构建及其生物学特性研究
为了验证两个痘苗病毒(Vaccinia virus,VV)强启动子P11和P28在重组猪痘病毒中的活性,构建了一个载体系统。利用这个系统获得了两个重组猪痘病毒rSPV-Z11和rSPV-Z28,并对这两个重组病毒的生物学特性进行了研究。在这个系统中,SPV基因组中SPV020和SPV021两基因间的366bp非编码区作为产生重组猪痘病毒的一个新的外源基因插入位点,大肠杆菌的lacZ基因作为一个显性筛选标记。获得的重组病毒用PCR和SDS-PAGE进行了鉴定,并对重组病毒在PK-15细胞中的增殖能力和亲本毒株进行了比较,同时我们也分析了重组病毒的遗传稳定性。结果显示,lacZ基因在重组病毒中稳定存在并能得到有效表达,重组病毒的滴度及蚀斑大小和亲本病毒差异不大,说明重组病毒性状稳定,该366bp非编码区的部分删除对病毒增殖影响不大,并且启动子P11和P28在重组病毒中有很强的活性,适合用于构建疫苗用的重组猪痘病毒。
3表达绿色荧光蛋白的重组猪痘病毒的构建及其在鼠源细胞系中的复制和表达
为了探讨小鼠作为猪痘病毒载体疫苗免疫学评价模型的可能性,构建了一个表达绿色荧光蛋白(Green fluorescent protein, GFP)的重组猪痘病毒rSPV-G28,并对重组病毒在鼠源细胞系LLC和Hepal-6中的复制和表达情况进行了研究。结果显示,rSPV-G28在这两个鼠源细胞中能够有效表达绿色荧光蛋白,并且重组病毒能在LLC细胞中复制并产生子代病毒,表明小鼠可作为猪痘病毒载体疫苗免疫学评价的动物模型。
4表达猪链球菌2型nrp基因片段的重组猪痘病毒的构建及免疫学评价
为了探讨SPV作为链球菌疫苗载体的潜力,构建了一个用于获得表达外源基因的重组猪痘病毒的载体系统,并用这个系统得到了一个表达猪链球菌2型mrp基因片段的重组猪痘病毒rSPV-MRP。通过PCR、western blotting和间接免疫荧光检测对rSPV-MRP进行了鉴定。经肌肉注射,分别用rSPV-MRP、SS2灭活疫苗(阳性对照)、SPV亲本病毒(阴性对照)及PBS(空白对照)给CD1小鼠免疫3次。在最后一次免疫后的第14天,用致死剂量或亚致死剂量的SS2强毒菌株ZY05719攻击CD1小鼠。结果显示,rSPV-MRP免疫组60%的小鼠存活,显著高于阴性对照组(P<0.05)。并且,rSPV-MRP免疫组的小鼠各器官细菌含量显著低于阴性对照组(P<0.05)rSPV-MRP免疫组的MRP特异性抗体滴度在检测的所有时间点都显著高于对照组(P<0.001)。这些数据表明,rSPV-MRP能显著保护CD1小鼠抵抗SS2强毒菌株的感染。因此,重组猪痘病毒有望成为猪链球菌疫苗用于预防猪发生链球菌感染。
5共表达猪链球菌2型SLY和MRP重组猪痘病毒的构建及其在CD1小鼠模型中的保护效率研究
利用GFP基因作为筛选标记构建了一个用于获得表达外源基因的重组猪痘病毒的载体系统,并用这个系统得到了两个表达SS2保护性抗原的重组猪痘病毒rSPV-SLY和rSPV-SLY-MRP。通过肌肉注射,分别用rSPV-SLY、rSPV-SLY-MRP、SS2灭活疫苗(阳性对照)、SPV亲本病毒(阴性对照)及PBS(空白对照)给CD1小鼠免疫3次。在最后一次免疫后的第14天,用致死剂量或亚致死剂量的SS2强毒菌株ZY05719攻击CD1小鼠。分别在免疫的0、7、14、21、28、35、42及49天采血用于测定小鼠的SLY和MRP特异性抗体水平。结果显示,重组病毒免疫组的特异性抗体在一免后的第7天就显著升高,且在加强免疫后持续上升。在免疫后的所有测定点,重组病毒免疫组的抗体滴度均显著高于阴性对照组(P<0.001),也明显高于阳性对照组(P<0.05)。数据还显示,重组病毒免疫组的小鼠各器官细菌含量显著低于阴性对照组(P<0.05)；rSPV-SLY免疫组和rSPV-SLY-MRP免疫组的攻毒保护率分别70%和100%。这些数据表明,重组猪痘病毒rSPV-SLY和rSPV-SLY-MRP能显著保护CD1小鼠抵抗SS2强毒菌株的感染,可作为猪链球菌疫苗的候选物。
6共表达猪链球菌2型ECE、MRP和SLY重组猪痘病毒的构建及其在CD1小鼠模型中的保护效率研究
利用猪痘病毒作为载体构建了三个表达SS2保护性抗原的重组病毒rSPV-ECE、 rSPV-ECE-SLY和rSPV-ECE-MRP-SLY.经肌肉注射,分别用rSPV-ECE、 rSPV-ECE-SLY、rSPV-ECE-MRP-SLY、SS2灭活疫苗(阳性对照)、SPV亲本病毒(阴性对照)及PBS(空白对照)给CD1小鼠免疫3次。在最后一次免疫后的第14天,用致死剂量或亚致死剂量的SS2强毒菌株ZY05719攻击CD1小鼠。分别在免疫的0、7、14、21、28、35、42及49天采血用于测定SS2保护性抗原的特异性抗体水平。结果显示,重组病毒免疫组的特异性抗体在一免后的第7天就显著升高,且在加强免疫后持续上升。在免疫后的所有测定点,重组病毒免疫组的抗体滴度均显著高于阴性对照组(P<0.001),也明显高于阳性对照组(P<0.05)。数据还显示,重组病毒免疫组的小鼠各器官细菌含量显著低于阴性对照组(P<0.05)；rSPV-ECE免疫组的攻毒保护率为60%,rSPV-ECE-SLY免疫组和rSPV-ECE-MRP-SLY免疫组的攻毒保护率均为100%。这些数据表明,表达SS2保护性抗原的重组猪痘病毒能显著保护CD1小鼠抵抗SS2强毒菌株的感染,可作为猪链球菌疫苗的候选物。
Streptococcus suis type2(SS2) is a major swine pathogen responsible for a wide range of diseases, including meningitis, arthritis, endocarditis, pneumonia, and septicaemia with sudden death. Moreover, SS2is an agent of zoonosis that has the potential to afflict those who are in close contact with infected pigs or pork-derived products. Swinepox virus (SPV) infects only swine. Natural SPV infections are typically mild and occasionally accompanied by localized skin lesions that heal naturally. SPV is well suited for the development of recombinant vaccines, because of its biological and clinical safety, large packaging capacity for recombinant DNA, and its ability to induce solid protective immunity. In this study, we constructed several recombinant SPVs expressing protective antigens of SS2, using SPV as the delivery vehicle. Furthermore, we assessed immunogenicity of these recombinant viruses.
1. The isolation of SPV and the serosurvey of swinepox
A strain of SPV was isolated from the pigs that showed typical evidence of the pox infection. Virus isolations were performed with the mixtures of encrusted cutaneous material and biopsied skin lesions. Three DNA fragments including unique sequence of SPV were amplified and sequenced, nucleotide sequence homology was91%,96%and99%respectively, when compared to those of the SPV17077-99strain. Furthermore, to investigate the epidemic status of swinepox, serosurvey of swinepox was conducted by agar gel diffusion precipitation test on1004adult swine serum samples collected from Jiangxi, Anhui, Hubei, Jiangsu, Guangdong and Shanghai. The results indicated that SPV infection was rarely present and only40(=4percent) of these serum samples contained anti-SPV antibodies. However, these positive samples were distributed in all six regions surveyed.
2. Construction and characterization of recombinant SPVs expressing lacZ gene
To test the activity of vaccinia virus (VV) late promoters P11and P28in the recombinant SPV, a vector was developed. We used this system to produce two recombinant viruses: rSPV-Z11and rSPV-Z28, and characterized replication and expression of the recombinant virus. In this system, the366bp non-coding region between the SPV20gene and the SPV21gene in the SPV genome was used as a novel insertion locus for generating recombinant SPV, and a dominant selection procedure based on lacZ gene expression was developed for recombinant virus isolation. Two recombinant viruses were identified by PCR and SDS-PAGE, and their replication were compared with the wild-type virus. We also assessed genetic stability of recombinant viruses. The results demonstrated that lacZ gene expression from two recombinant viruses was stable over ten passages and the generated viral titer and plaque area was comparable to wild-type SPV. From these observations, we concluded that the recombinant viruses had good genetic stability and the partial deletion of the intergene region was dispensable for growth in PK-15cells. Furthermore, the activity of promoters P11and P28was very strong in the recombinant SPV and suitable to the production of recombinant vaccines.
3. Replication and expression of a recombinant SPV expressing green fluorescent protein in two murine cell lines
To explore the potential of the mouse as an animal model for the immunological evaluation of SPV-based vaccines, a recombinant virus expressing green fluorescent protein (GFP), designated rSPV-G28, was produced, and we characterized replication and expression of the recombinant virus in two murine cell lines, LLC and Hepal-6. Our results showed that murine cells were susceptible to infection by SPV and supported expression of GFP, and SPV viral DNA was replicated in LLC cells and infectious virus was recovered. These results suggest that the mouse may have potential as an animal model for the immunological evaluation of SPV-based vaccines.
4. Construction and immunogenicity of a recombinant SPV expressing truncated MRP of SS2
To explore the potential of the SPV as vector for Streptococcus suis vaccines, a vector system was developed for the construction of a recombinant SPV carrying bacterial genes. Using this system, a recombinant virus expressing truncated muramidase-released protein (MRP) of SS2, designated rSPV-MRP, was produced and identified by PCR, western blotting and immunofluorescence assays. After immunized intramuscularly with rSPV-MRP, SS2inactive vaccine (positive control), wild-type SPV (negative control) and PBS (blank control) respectively, all CD1mice were challenged with a lethal dose or a sublethal dose of SS2highly virulent strain ZY05719. Immunization with rSPV-MRP resulted in60%survival and significantly protected mice against a lethal dose of the highly virulent SS2strain, compared with the negative control (P<0.05). Our data indicate that animals immunized with rSPV-MRP had a significantly reduced bacterial burden in all organs examined, compared to negative controls (P<0.05). Antibody titers of the rSPV-MRP-vaccinated group were significantly higher (P<0.001), when compared to negative controls. Antibody titers were also significantly higher in the vaccinated group at all time points post-vaccination (P<0.001), compared with the positive controls. The results demonstrated that the rSPV-MRP provided mice with significant protection from systemic SS2infection. It suggested that SPV recombinants have the potential as S. suis vaccines for the use in pigs.
5. Development of recombinant SPVs coexpressing SLY and MRP of SS2: immunogenicity and efficacy studies in CD1mice model
We developed a vector system for the construction of a recombinant SPV carrying foreign genes, using GFP gene as a dominant selection marker. We used this system to produce two recombinant viruses expressing protective antigens of SS2, rSPV-SLY and rSPV-SLY-MRP. CD1mice were immunized intramuscularly three times with rSPV-SLY, rSPV-SLY-MRP, SS2inactive vaccine (positive control), wild-type SPV (negative control), and PBS (blank control). Two weeks after the last immunization, all mice were challenged with lethal or sublethal doses of the highly virulent SS2strain ZY05719. Sera were examined for the specific antibody titers using enzyme-linked immunosorbent assay (ELISA). Specific antibody titers of mice vaccinated with recombinant viruses increased dramatically at day7post-vaccination, and continued to increase after the boost. Antibody titers were significantly higher (P<0.001), when compared to negative controls. Antibody titers were also significantly higher at all time points post-vaccination (P<0.05), compared with the positive controls. Our data indicate that animals immunized with recombinant viruses had a significantly reduced bacterial burden in all organs examined, compared to negative control (P<0.05). Immunization with rSPV-SLY resulted in70%survival, and immunization with rSPV-SLY-MRP resulted in100%survival. Both rSPV-SLY (P<0.05) and rSPV-SLY-MRP (P<0.001) significantly protected mice against a lethal dose of the highly virulent SS2strain, compared with the negative control. Our results suggest that rSPV-SLY and rSPV-SLY-MRP provide mice with significant protection from systemic SS2infection and can take as vaccine candidates of SS2.
6. Development of recombinant SPVs coexpressing ECE, MRP and SLY of SS2: immunogenicity and efficacy studies in CD1mice model
We generated three recombinant SPVs:rSPV-ECE、rSPV-ECE-SLY and rSPV-ECE-MRP-SLY, using SPV as the delivery vehicle. CD1mice were immunized intramuscularly three times with rSPV-ECE、rSPV-ECE-SLY, rSPV-ECE-MRP-SLY, SS2inactive vaccine (positive control), wild-type SPV (negative control), and PBS (blank control). Two weeks after the last immunization, all mice were challenged with lethal or sublethal doses of the highly virulent SS2strain ZY05719. Sera were examined for the specific antibody titers from all groups using ELISA. Specific antibody titers of mice vaccinated with recombinant SPVs increased dramatically at day7post-vaccination, and continued to increase after the boost. Antibody titers were significantly higher (P<0.001), when compared to negative controls. Antibody titers were also significantly higher at all time points post-vaccination (P<0.05), compared with the positive controls. Our data indicate that animals immunized with recombinant SPVs had a significantly reduced bacterial burden in all organs examined, compared to negative control (P<0.05). Immunization with rSPV-ECE resulted in60%survival, and immunization with rSPV-ECE-SLY or rSPV-ECE-MRP-SLY resulted in100%survival. Our results suggest that rSPV-ECE、rSPV-ECE-SLY and rSPV-ECE-MRP-SLY provide mice with significant protection from systemic SS2infection and can take as vaccine candidates of SS2.
1SPV的分离及猪痘的血清学调查
用PK-15细胞在猪痘发病猪的痂皮和脓疱中分离到一株SPV。对包含SPV特异性序列在内的三段核酸序列进行了扩增和测序,与SPV17077-99株相比,三段序列的核苷酸同源性分别为91%、96%和99%。此外,为了了解猪痘的流行现状,利用琼脂扩散试验对来自江西、安徽、湖北、江苏、广东及上海共1004份成年猪血清进行了猪痘血清学调查。结果表明,猪痘在猪群中较少发生,在被检测的1004份样品中只有40份阳性,阳性率仅为4%,但被调查的六个地区都有分布。
2表达lacZ基因重组猪痘病毒的构建及其生物学特性研究
为了验证两个痘苗病毒(Vaccinia virus,VV)强启动子P11和P28在重组猪痘病毒中的活性,构建了一个载体系统。利用这个系统获得了两个重组猪痘病毒rSPV-Z11和rSPV-Z28,并对这两个重组病毒的生物学特性进行了研究。在这个系统中,SPV基因组中SPV020和SPV021两基因间的366bp非编码区作为产生重组猪痘病毒的一个新的外源基因插入位点,大肠杆菌的lacZ基因作为一个显性筛选标记。获得的重组病毒用PCR和SDS-PAGE进行了鉴定,并对重组病毒在PK-15细胞中的增殖能力和亲本毒株进行了比较,同时我们也分析了重组病毒的遗传稳定性。结果显示,lacZ基因在重组病毒中稳定存在并能得到有效表达,重组病毒的滴度及蚀斑大小和亲本病毒差异不大,说明重组病毒性状稳定,该366bp非编码区的部分删除对病毒增殖影响不大,并且启动子P11和P28在重组病毒中有很强的活性,适合用于构建疫苗用的重组猪痘病毒。
3表达绿色荧光蛋白的重组猪痘病毒的构建及其在鼠源细胞系中的复制和表达
为了探讨小鼠作为猪痘病毒载体疫苗免疫学评价模型的可能性,构建了一个表达绿色荧光蛋白(Green fluorescent protein, GFP)的重组猪痘病毒rSPV-G28,并对重组病毒在鼠源细胞系LLC和Hepal-6中的复制和表达情况进行了研究。结果显示,rSPV-G28在这两个鼠源细胞中能够有效表达绿色荧光蛋白,并且重组病毒能在LLC细胞中复制并产生子代病毒,表明小鼠可作为猪痘病毒载体疫苗免疫学评价的动物模型。
4表达猪链球菌2型nrp基因片段的重组猪痘病毒的构建及免疫学评价
为了探讨SPV作为链球菌疫苗载体的潜力,构建了一个用于获得表达外源基因的重组猪痘病毒的载体系统,并用这个系统得到了一个表达猪链球菌2型mrp基因片段的重组猪痘病毒rSPV-MRP。通过PCR、western blotting和间接免疫荧光检测对rSPV-MRP进行了鉴定。经肌肉注射,分别用rSPV-MRP、SS2灭活疫苗(阳性对照)、SPV亲本病毒(阴性对照)及PBS(空白对照)给CD1小鼠免疫3次。在最后一次免疫后的第14天,用致死剂量或亚致死剂量的SS2强毒菌株ZY05719攻击CD1小鼠。结果显示,rSPV-MRP免疫组60%的小鼠存活,显著高于阴性对照组(P<0.05)。并且,rSPV-MRP免疫组的小鼠各器官细菌含量显著低于阴性对照组(P<0.05)rSPV-MRP免疫组的MRP特异性抗体滴度在检测的所有时间点都显著高于对照组(P<0.001)。这些数据表明,rSPV-MRP能显著保护CD1小鼠抵抗SS2强毒菌株的感染。因此,重组猪痘病毒有望成为猪链球菌疫苗用于预防猪发生链球菌感染。
5共表达猪链球菌2型SLY和MRP重组猪痘病毒的构建及其在CD1小鼠模型中的保护效率研究
利用GFP基因作为筛选标记构建了一个用于获得表达外源基因的重组猪痘病毒的载体系统,并用这个系统得到了两个表达SS2保护性抗原的重组猪痘病毒rSPV-SLY和rSPV-SLY-MRP。通过肌肉注射,分别用rSPV-SLY、rSPV-SLY-MRP、SS2灭活疫苗(阳性对照)、SPV亲本病毒(阴性对照)及PBS(空白对照)给CD1小鼠免疫3次。在最后一次免疫后的第14天,用致死剂量或亚致死剂量的SS2强毒菌株ZY05719攻击CD1小鼠。分别在免疫的0、7、14、21、28、35、42及49天采血用于测定小鼠的SLY和MRP特异性抗体水平。结果显示,重组病毒免疫组的特异性抗体在一免后的第7天就显著升高,且在加强免疫后持续上升。在免疫后的所有测定点,重组病毒免疫组的抗体滴度均显著高于阴性对照组(P<0.001),也明显高于阳性对照组(P<0.05)。数据还显示,重组病毒免疫组的小鼠各器官细菌含量显著低于阴性对照组(P<0.05)；rSPV-SLY免疫组和rSPV-SLY-MRP免疫组的攻毒保护率分别70%和100%。这些数据表明,重组猪痘病毒rSPV-SLY和rSPV-SLY-MRP能显著保护CD1小鼠抵抗SS2强毒菌株的感染,可作为猪链球菌疫苗的候选物。
6共表达猪链球菌2型ECE、MRP和SLY重组猪痘病毒的构建及其在CD1小鼠模型中的保护效率研究
利用猪痘病毒作为载体构建了三个表达SS2保护性抗原的重组病毒rSPV-ECE、 rSPV-ECE-SLY和rSPV-ECE-MRP-SLY.经肌肉注射,分别用rSPV-ECE、 rSPV-ECE-SLY、rSPV-ECE-MRP-SLY、SS2灭活疫苗(阳性对照)、SPV亲本病毒(阴性对照)及PBS(空白对照)给CD1小鼠免疫3次。在最后一次免疫后的第14天,用致死剂量或亚致死剂量的SS2强毒菌株ZY05719攻击CD1小鼠。分别在免疫的0、7、14、21、28、35、42及49天采血用于测定SS2保护性抗原的特异性抗体水平。结果显示,重组病毒免疫组的特异性抗体在一免后的第7天就显著升高,且在加强免疫后持续上升。在免疫后的所有测定点,重组病毒免疫组的抗体滴度均显著高于阴性对照组(P<0.001),也明显高于阳性对照组(P<0.05)。数据还显示,重组病毒免疫组的小鼠各器官细菌含量显著低于阴性对照组(P<0.05)；rSPV-ECE免疫组的攻毒保护率为60%,rSPV-ECE-SLY免疫组和rSPV-ECE-MRP-SLY免疫组的攻毒保护率均为100%。这些数据表明,表达SS2保护性抗原的重组猪痘病毒能显著保护CD1小鼠抵抗SS2强毒菌株的感染,可作为猪链球菌疫苗的候选物。
Streptococcus suis type2(SS2) is a major swine pathogen responsible for a wide range of diseases, including meningitis, arthritis, endocarditis, pneumonia, and septicaemia with sudden death. Moreover, SS2is an agent of zoonosis that has the potential to afflict those who are in close contact with infected pigs or pork-derived products. Swinepox virus (SPV) infects only swine. Natural SPV infections are typically mild and occasionally accompanied by localized skin lesions that heal naturally. SPV is well suited for the development of recombinant vaccines, because of its biological and clinical safety, large packaging capacity for recombinant DNA, and its ability to induce solid protective immunity. In this study, we constructed several recombinant SPVs expressing protective antigens of SS2, using SPV as the delivery vehicle. Furthermore, we assessed immunogenicity of these recombinant viruses.
1. The isolation of SPV and the serosurvey of swinepox
A strain of SPV was isolated from the pigs that showed typical evidence of the pox infection. Virus isolations were performed with the mixtures of encrusted cutaneous material and biopsied skin lesions. Three DNA fragments including unique sequence of SPV were amplified and sequenced, nucleotide sequence homology was91%,96%and99%respectively, when compared to those of the SPV17077-99strain. Furthermore, to investigate the epidemic status of swinepox, serosurvey of swinepox was conducted by agar gel diffusion precipitation test on1004adult swine serum samples collected from Jiangxi, Anhui, Hubei, Jiangsu, Guangdong and Shanghai. The results indicated that SPV infection was rarely present and only40(=4percent) of these serum samples contained anti-SPV antibodies. However, these positive samples were distributed in all six regions surveyed.
2. Construction and characterization of recombinant SPVs expressing lacZ gene
To test the activity of vaccinia virus (VV) late promoters P11and P28in the recombinant SPV, a vector was developed. We used this system to produce two recombinant viruses: rSPV-Z11and rSPV-Z28, and characterized replication and expression of the recombinant virus. In this system, the366bp non-coding region between the SPV20gene and the SPV21gene in the SPV genome was used as a novel insertion locus for generating recombinant SPV, and a dominant selection procedure based on lacZ gene expression was developed for recombinant virus isolation. Two recombinant viruses were identified by PCR and SDS-PAGE, and their replication were compared with the wild-type virus. We also assessed genetic stability of recombinant viruses. The results demonstrated that lacZ gene expression from two recombinant viruses was stable over ten passages and the generated viral titer and plaque area was comparable to wild-type SPV. From these observations, we concluded that the recombinant viruses had good genetic stability and the partial deletion of the intergene region was dispensable for growth in PK-15cells. Furthermore, the activity of promoters P11and P28was very strong in the recombinant SPV and suitable to the production of recombinant vaccines.
3. Replication and expression of a recombinant SPV expressing green fluorescent protein in two murine cell lines
To explore the potential of the mouse as an animal model for the immunological evaluation of SPV-based vaccines, a recombinant virus expressing green fluorescent protein (GFP), designated rSPV-G28, was produced, and we characterized replication and expression of the recombinant virus in two murine cell lines, LLC and Hepal-6. Our results showed that murine cells were susceptible to infection by SPV and supported expression of GFP, and SPV viral DNA was replicated in LLC cells and infectious virus was recovered. These results suggest that the mouse may have potential as an animal model for the immunological evaluation of SPV-based vaccines.
4. Construction and immunogenicity of a recombinant SPV expressing truncated MRP of SS2
To explore the potential of the SPV as vector for Streptococcus suis vaccines, a vector system was developed for the construction of a recombinant SPV carrying bacterial genes. Using this system, a recombinant virus expressing truncated muramidase-released protein (MRP) of SS2, designated rSPV-MRP, was produced and identified by PCR, western blotting and immunofluorescence assays. After immunized intramuscularly with rSPV-MRP, SS2inactive vaccine (positive control), wild-type SPV (negative control) and PBS (blank control) respectively, all CD1mice were challenged with a lethal dose or a sublethal dose of SS2highly virulent strain ZY05719. Immunization with rSPV-MRP resulted in60%survival and significantly protected mice against a lethal dose of the highly virulent SS2strain, compared with the negative control (P<0.05). Our data indicate that animals immunized with rSPV-MRP had a significantly reduced bacterial burden in all organs examined, compared to negative controls (P<0.05). Antibody titers of the rSPV-MRP-vaccinated group were significantly higher (P<0.001), when compared to negative controls. Antibody titers were also significantly higher in the vaccinated group at all time points post-vaccination (P<0.001), compared with the positive controls. The results demonstrated that the rSPV-MRP provided mice with significant protection from systemic SS2infection. It suggested that SPV recombinants have the potential as S. suis vaccines for the use in pigs.
5. Development of recombinant SPVs coexpressing SLY and MRP of SS2: immunogenicity and efficacy studies in CD1mice model
We developed a vector system for the construction of a recombinant SPV carrying foreign genes, using GFP gene as a dominant selection marker. We used this system to produce two recombinant viruses expressing protective antigens of SS2, rSPV-SLY and rSPV-SLY-MRP. CD1mice were immunized intramuscularly three times with rSPV-SLY, rSPV-SLY-MRP, SS2inactive vaccine (positive control), wild-type SPV (negative control), and PBS (blank control). Two weeks after the last immunization, all mice were challenged with lethal or sublethal doses of the highly virulent SS2strain ZY05719. Sera were examined for the specific antibody titers using enzyme-linked immunosorbent assay (ELISA). Specific antibody titers of mice vaccinated with recombinant viruses increased dramatically at day7post-vaccination, and continued to increase after the boost. Antibody titers were significantly higher (P<0.001), when compared to negative controls. Antibody titers were also significantly higher at all time points post-vaccination (P<0.05), compared with the positive controls. Our data indicate that animals immunized with recombinant viruses had a significantly reduced bacterial burden in all organs examined, compared to negative control (P<0.05). Immunization with rSPV-SLY resulted in70%survival, and immunization with rSPV-SLY-MRP resulted in100%survival. Both rSPV-SLY (P<0.05) and rSPV-SLY-MRP (P<0.001) significantly protected mice against a lethal dose of the highly virulent SS2strain, compared with the negative control. Our results suggest that rSPV-SLY and rSPV-SLY-MRP provide mice with significant protection from systemic SS2infection and can take as vaccine candidates of SS2.
6. Development of recombinant SPVs coexpressing ECE, MRP and SLY of SS2: immunogenicity and efficacy studies in CD1mice model
We generated three recombinant SPVs:rSPV-ECE、rSPV-ECE-SLY and rSPV-ECE-MRP-SLY, using SPV as the delivery vehicle. CD1mice were immunized intramuscularly three times with rSPV-ECE、rSPV-ECE-SLY, rSPV-ECE-MRP-SLY, SS2inactive vaccine (positive control), wild-type SPV (negative control), and PBS (blank control). Two weeks after the last immunization, all mice were challenged with lethal or sublethal doses of the highly virulent SS2strain ZY05719. Sera were examined for the specific antibody titers from all groups using ELISA. Specific antibody titers of mice vaccinated with recombinant SPVs increased dramatically at day7post-vaccination, and continued to increase after the boost. Antibody titers were significantly higher (P<0.001), when compared to negative controls. Antibody titers were also significantly higher at all time points post-vaccination (P<0.05), compared with the positive controls. Our data indicate that animals immunized with recombinant SPVs had a significantly reduced bacterial burden in all organs examined, compared to negative control (P<0.05). Immunization with rSPV-ECE resulted in60%survival, and immunization with rSPV-ECE-SLY or rSPV-ECE-MRP-SLY resulted in100%survival. Our results suggest that rSPV-ECE、rSPV-ECE-SLY and rSPV-ECE-MRP-SLY provide mice with significant protection from systemic SS2infection and can take as vaccine candidates of SS2.
引文
[1]Cheville NF. Immunofluorescent and morphologic studies on swinepox. Pathologia veterinaria 1966;3(5):556-64.
[2]Conroy JD, Meyer RC. Electron microscopy of swinepox virus in germfree pigs and in cell culture. American journal of veterinary research 1971 Dec;32(12):2021-32.
[3]Teppema JS, De Boer GF. Ultrastructural aspects of experimental swinepox with special reference to inclusion bodies. Archives of virology 1975;49(2-3):151-63.
[4]De Boer GF. Swinepox. Virus isolation, experimental infections and the differentiation from vaccinia virus infections. Archives of virology 1975;49(2-3):141-50.
[5]Massung RF, Moyer RW. The molecular biology of swinepox virus. Ⅱ. The infectious cycle. Virology 1991 Jan;180(1):355-64.
[6]Datt NS. Comparative Studies of Pigpox and Vaccinia Viruses. Ⅰ. Host Range Pathogenicity. Journal of comparative pathology 1964 Jan;74:62-9.
[7]Datt NS. Comparative Studies of Pigpox and Vaccinia Viruses. Ii. Serological Relationship. Journal of comparative pathology 1964 Jan;74:70-80.
[8]Shope RE. Swine pox. Archives of virology 1940; 1 (4):457-67.
[9]Afonso CL, Tulman ER, Lu Z, et al. The genome of swinepox virus. Journal of virology 2002 Jan;76(2):783-90.
[10]Schnitzlein WM, Tripathy DN. Identification and nucleotide sequence of the thymidine kinase gene of swinepox virus. Virology 1991 Apr;181(2):727-32.
[11]Kasza L, Bohl EH, Jones DO. Isolation and cultivation of swine pox virus in primary cell cultures of swine origin. American journal of veterinary research 1960 Mar;21:269-73.
[12]Delhon G, Tulman E, Afonso C, et al. Genus Suipoxvirus. Poxviruses,2007:203-15.
[13]Paton DJ, Brown IH, Fitton J, et al. Congenital pig pox:a case report. The Veterinary record 1990 Aug 25;127(8):204.
[14]Jubb TF, Ellis TM, Peet RL, et al. Swinepox in pigs in northern Western Australia. Australian veterinary journal 1992 Apr;69(4):99.
[15]Borst GH, Kimman TG, Gielkens AL, et al. Four sporadic cases of congenital swinepox. The Veterinary record 1990 Jul 21;127(3):61-3.
[16]Kim UH, Mukhajonpan V, Nii S, et al. Ultrastructural study of cell cultures infected with swinepox and orf viruses. Biken journal 1977 Jun;20(2):57-67.
[17]Olufemi BE, Ayoade GO, Ikede BO, et al. Swine pox in Nigeria. The Veterinary record 1981 Sep 26;109(13):278-80.
[18]Kasza L, Griesemer RA. Experimental swine pox. American journal of veterinary research 1962 May;23:443-51.
[19]Meyer RC, Conroy JD. Experimental swinepox in gnotobiotic piglets. Research in veterinary science 1972 Jul;13(4):334-8.
[20]Miller RB, Olson LD. Experimental induction of cutaneous streptococcal abscesses in swine as a sequela to swinepox. American journal of veterinary research 1980 Mar;41(3):341-7.
[21]Massung RF, Jayarama V, Moyer RW. DNA sequence analysis of conserved and unique regions of swinepox virus:identification of genetic elements supporting phenotypic observations including a novel G protein-coupled receptor homologue. Virology 1993 Dec; 197(2):511-28.
[22]Brunetti CR, Paulose-Murphy M, Singh R, et al. A secreted high-affinity inhibitor of human TNF from Tanapox virus. Proceedings of the National Academy of Sciences of the United States of America 2003 Apr 15;100(8):4831-6.
[23]Bartee E, Mansouri M, Hovey Nerenberg BT, et al. Downregulation of major histocompatibility complex class I by human ubiquitin ligases related to viral immune evasion proteins. Journal of virology 2004 Feb;78(3):1109-20.
[24]Sanderson CM, Parkinson JE, Hollinshead M, et al. Overexpression of the vaccinia virus A38L integral membrane protein promotes Ca2+ influx into infected cells. Journal of virology 1996 Feb;70(2):905-14.
[25]Najarro P, Lee HJ, Fox J, et al. Yaba-like disease virus protein 7L is a cell-surface receptor for chemokine CCL1. The Journal of general virology 2003 Dec;84(Pt 12):3325-36.
[26]Guerin JL, Gelfi J, Boullier S, et al. Myxoma virus leukemia-associated protein is responsible for major histocompatibility complex class I and Fas-CD95 down-regulation and defines scrapins, a new group of surface cellular receptor abductor proteins. Journal of virology 2002 Mar;76(6):2912-23.
[27]Mansouri M, Bartee E, Gouveia K, et al. The PHD/LAP-domain protein M153R of myxomavirus is a ubiquitin ligase that induces the rapid internalization and lysosomal destruction of CD4. Journal of virology 2003 Jan;77(2):1427-40.
[28]Langland JO, Jacobs BL. The role of the PKR-inhibitory genes, E3L and K3L, in determining vaccinia virus host range. Virology 2002 Jul 20;299(1):133-41.
[29]Smith GL, Chan YS, Howard ST. Nucleotide sequence of 42 kbp of vaccinia virus strain WR from near the right inverted terminal repeat. The Journal of general virology 1991 Jun;72 (Pt 6):1349-76.
[30]Bowie AG, Haga IR. The role of Toll-like receptors in the host response to viruses. Molecular immunology 2005 May;42(8):859-67.
[31]Stack J, Haga IR, Schroder M, et al. Vaccinia virus protein A46R targets multiple Toll-like-interleukin-1 receptor adaptors and contributes to virulence. The Journal of experimental medicine 2005 Mar 21;201 (6):1007-18.
[32]DiPerna G, Stack J, Bowie AG, et al. Poxvirus protein NIL targets the I-kappaB kinase complex, inhibits signaling to NF-kappaB by the tumor necrosis factor superfamily of receptors, and inhibits NF-kappaB and IRF3 signaling by toll-like receptors. The Journal of biological chemistry 2004 Aug 27;279(35):36570-8.
[33]Everett H, Barry M, Lee SF, et al. M11L:a novel mitochondria-localized protein of myxoma virus that blocks apoptosis of infected leukocytes. The Journal of experimental medicine 2000 May 1;191(9):1487-98.
[34]Perkus ME, Goebel SJ, Davis SW, et al. Vaccinia virus host range genes. Virology 1990 Nov;179(1):276-86.
[35]Betakova T, Wolffe EJ, Moss B. The vaccinia virus A14.5L gene encodes a hydrophobic 53-amino-acid virion membrane protein that enhances virulence in mice and is conserved among vertebrate poxviruses. Journal of virology 2000 May;74(9):4085-92.
[36]Senkevich TG, Koonin EV, Buller RM. A poxvirus protein with a RING zinc finger motif is of crucial importance for virulence. Virology 1994 Jan;198(1):118-28.
[37]Senkevich TG, Wolffe EJ, Buller RM. Ectromelia virus RING finger protein is localized in virus factories and is required for virus replication in macrophages. Journal of virology 1995 Jul;69(7):4103-11.
[38]Nerenberg BT, Taylor J, Bartee E, et al. The poxviral RING protein p28 is a ubiquitin ligase that targets ubiquitin to viral replication factories. Journal of virology 2005 Jan;79(1):597-601.
[39]Gillard S, Spehner D, Drillien R, et al. Localization and sequence of a vaccinia virus gene required for multiplication in human cells. Proceedings of the National Academy of Sciences of the United States of America 1986 Aug;83(15):5573-7.
[40]Mossman K, Lee SF, Barry M, et al. Disruption of M-T5, a novel myxoma virus gene member of poxvirus host range superfamily, results in dramatic attenuation of myxomatosis in infected European rabbits. Journal of virology 1996 Jul;70(7):4394-410.
[41]Spehner D, Gillard S, Drillien R, et al. A cowpox virus gene required for multiplication in Chinese hamster ovary cells. Journal of virology 1988 Apr;62(4):1297-304.
[42]Camus-Bouclainville C, Fiette L, Bouchiha S, et al. A virulence factor of myxoma virus colocalizes with NF-kappaB in the nucleus and interferes with inflammation. Journal of virology 2004 Mar;78(5):2510-6.
[43]Johnston JB, Wang G, Barrett JW, et al. Myxoma virus M-T5 protects infected cells from the stress of cell cycle arrest through its interaction with host cell cullin-1. Journal of virology 2005 Aug;79(16):10750-63.
[44]Antoine G, Scheiflinger F, Dorner F, et al. The complete genomic sequence of the modified vaccinia Ankara strain:comparison with other orthopoxviruses. Virology 1998 May 10;244(2):365-96.
[45]Shchelkunov SN, Safronov PF, Totmenin AV, et al. The genomic sequence analysis of the left and right species-specific terminal region of a cowpox virus strain reveals unique sequences and a cluster of intact ORFs for immunomodulatory and host range proteins. Virology 1998 Apr 10;243(2):432-60.
[46]Kochneva G, Kolosova I, Maksyutova T, et al. Effects of deletions of kelch-like genes on cowpox virus biological properties. Archives of virology 2005 Sep; 150(9):1857-70.
[47]Tulman ER, Afonso CL, Lu Z, et al. The genomes of sheeppox and goatpox viruses. Journal of virology 2002 Jun;76(12):6054-61.
[48]Pires de Miranda M, Reading PC, Tscharke DC, et al. The vaccinia virus kelch-like protein C2L affects calcium-independent adhesion to the extracellular matrix and inflammation in a murine intradermal model. The Journal of general virology 2003 Sep;84(Pt 9):2459-71.
[49]Mackett M, Smith GL, Moss B. General method for production and selection of infectious vaccinia virus recombinants expressing foreign genes. Journal of virology 1984 Mar;49(3):857-64.
[50]van der Leek ML, Feller JA, Sorensen G, et al. Evaluation of swinepox virus as a vaccine vector in pigs using an Aujeszky's disease (pseudorabies) virus gene insert coding for glycoproteins gp50 and gp63. The Veterinary record 1994 Jan 1;134(1):13-8.
[51]Hahn J, Park SH, Song JY, et al. Construction of recombinant swinepox viruses and expression of the classical swine fever virus E2 protein. Journal of virological methods 2001 Apr;93(1-2):49-56.
[52]Winslow BJ, Cochran MD, Holzenburg A, et al. Replication and expression of a swinepox virus vector delivering feline leukemia virus Gag and Env to cell lines of swine and feline origin. Virus research 2003 Dec;98(1):1-15.
[53]Barcena J, Blasco R. Recombinant swinepox virus expressing beta-galactosidase:investigation of viral host range and gene expression levels in cell culture. Virology 1998 Apr 10;243(2):396-405.
[54]Winslow BJ, Kalabat DY, Brown SM, et al. Feline B7.1 and B7.2 proteins produced from swinepox virus vectors are natively processed and biologically active:potential for use as nonchemical adjuvants. Veterinary microbiology 2005 Nov 30;111(1-2):1-13.
[55]Domi A, Moss B. Engineering of a vaccinia virus bacterial artificial chromosome in Escherichia coli by bacteriophage lambda-based recombination. Nature methods 2005 Feb;2(2):95-7.
[56]Moss B. Genetically engineered poxviruses for recombinant gene expression, vaccination, and safety. Proceedings of the National Academy of Sciences of the United States of America 1996 Oct 15;93(21):11341-8.
[57]Paoletti E. Applications of pox virus vectors to vaccination:an update. Proceedings of the National Academy of Sciences of the United States of America 1996 Oct 15;93(21):11349-53.
[58]Yamanouchi K, Barrett T, Kai C. New approaches to the development of virus vaccines for veterinary use. Revue scientifique et technique (International Office of Epizootics) 1998 Dec;17(3):641-53.
[1]Chanter N, Jones PW, Alexander TJ. Meningitis in pigs caused by Streptococcus suis-a speculative review. Veterinary microbiology 1993 Jul;36(1-2):39-55.
[2]Staats JJ, Feder I, Okwumabua O, et al. Streptococcus suis:past and present. Veterinary research communications 1997 Aug;21(6):381-407.
[3]Gottschalk M, Segura M. The pathogenesis of the meningitis caused by Streptococcus suis:the unresolved questions. Veterinary microbiology 2000 Oct 1;76(3):259-72.
[4]陆承平,姚火春,范红结,et al.猪链球菌致病性研究及其公共卫生意义.中国预防医学杂志2006；7(4)：361-2.
[5]Gottschalk M. Streptococcus suis Infections in Humans:What is the prognosis for Western countries? (Part Ⅰ). Clinical Microbiology Newsletter 2010 Jun;32(12):89-96.
[6]Fittipaldi N, Fuller TE, Teel JF, et al. Serotype distribution and production of muramidase-released protein, extracellular factor and suilysin by field strains of Streptococcus suis isolated in the United States. Veterinary microbiology 2009 Nov 18;139(3-4):310-7.
[7]Gottschalk M. Streptococcus suis Infections in Humans:What is the prognosis for Western countries? (Part Ⅱ). Clinical Microbiology Newsletter 2010.
[8]Sriskandan S, Slater JD. Invasive disease and toxic shock due to zoonotic Streptococcus suis:an emerging infection in the East? PLoS medicine 2006 May;3(5):e187.
[9]陆承平.兽医微生物学(第四版).2007.
[10]Tang J, Wang C, Feng Y, et al. Streptococcal toxic shock syndrome caused by Streptococcus suis serotype 2. PLoS medicine 2006 May;3(5):e151.
[11]姚火春,陈国强.猪链球菌1998分离株病原特性鉴定.南京农业大学学报1999；22(2)：67-70.
[12]Holden MT, Hauser H, Sanders M, et al. Rapid evolution of virulence and drug resistance in the emerging zoonotic pathogen Streptococcus suis. PloS one 2009;4(7):e6072.
[13]Vecht U, Wisselink HJ, Jellema ML, et al. Identification of two proteins associated with virulence of Streptococcus suis type 2. Infection and immunity 1991 Sep;59(9):3156-62.
[14]Smith HE, Vecht U, Gielkens AL, et al. Cloning and nucleotide sequence of the gene encoding the 136-kilodalton surface protein (muramidase-released protein) of Streptococcus suis type 2. Infection and immunity 1992 Jun;60(6):2361-7.
[15]曾巧英,陆承平.猪链球菌2型溶菌酶释放蛋白的黏附作用.南京农业大学学报2002；25(4)：67-71.
[16]范红结,陆承平,唐家琪.猪链球菌2型mrp基因免疫功能片段的克隆、表达及动物试验.微生物学报2004；44(1)：54-7.
[17]范红结,陆承平,唐家琪.马链球菌兽疫亚种类M基因和猪链球菌2型mrp基因片段的融合表达及仔猪免疫试验.南京农业大学学报2003；26(4)：78-81.
[18]Smith HE, Reek FH, Vecht U, et al. Repeats in an extracellular protein of weakly pathogenic strains of Streptococcus suis type 2 are absent in pathogenic strains. Infection and immunity 1993 Aug;61(8):3318-26.
[19]Wisselink HJ, Vecht U, Stockhofe-Zurwieden N, et al. Protection of pigs against challenge with virulent Streptococcus suis serotype 2 strains by a muramidase-released protein and extracellular factor vaccine. The Veterinary record 2001 Apr 14;148(15):473-7.
[20]Jacobs AA, Loeffen PL, van den Berg AJ, et al. Identification, purification, and characterization of a thiol-activated hemolysin (suilysin) of Streptococcus suis. Infection and immunity 1994 May;62(5):1742-8.
[21]Gottschalk MG, Lacouture S, Dubreuil JD. Characterization of Streptococcus suis capsular type 2 haemolysin. Microbiology (Reading, England) 1995 Jan;141 (Pt 1):189-95.
[22]陈国强,姚火春.猪链球菌2型溶血毒素的产生条件及其特性分析.南京农业大学学报2000；23(3)：71-5.
[23]Staats JJ, Plattner BL, Stewart GC, et al. Presence of the Streptococcus suis suilysin gene and expression of MRP and EF correlates with high virulence in Streptococcus suis type 2 isolates. Veterinary microbiology 1999 Dec;70(3-4):201-11.
[24]Charland N, Nizet V, Rubens CE, et al. Streptococcus suis serotype 2 interactions with human brain microvascular endothelial cells. Infection and immunity 2000 Feb;68(2):637-43.
[25]Lalonde M, Segura M, Lacouture S, et al. Interactions between Streptococcus suis serotype 2 and different epithelial cell lines. Microbiology (Reading, England) 2000 Aug;146 (Pt 8):1913-21.
[26]Segura M, Gottschalk M. Streptococcus suis interactions with the murine macrophage cell line J774: adhesion and cytotoxicity. Infection and immunity 2002 Aug;70(8):4312-22.
[27]Norton PM, Rolph C, Ward PN, et al. Epithelial invasion and cell lysis by virulent strains of Streptococcus suis is enhanced by the presence of suilysin. FEMS immunology and medical microbiology 1999 Oct;26(1):25-35.
[28]Allen AG, Bolitho S, Lindsay H, et al. Generation and characterization of a defined mutant of Streptococcus suis lacking suilysin. Infection and immunity 2001 Apr;69(4):2732-5.
[29]Jacobs AA, van den Berg AJ, Loeffen PL. Protection of experimentally infected pigs by suilysin, the thiol-activated haemolysin of Streptococcus suis. The Veterinary record 1996 Sep 7;139(10):225-8.
[30]Liu L, Cheng G, Wang C, et al. Identification and experimental verification of protective antigens against Streptococcus suis serotype 2 based on genome sequence analysis. Current microbiology 2009 Jan;58(1):11-7.
[31]陈国强,陆承平,等.猪链球菌2型溶血素的提纯及其生物学特性.中国人兽共患病杂志2001；17(5)：75-7.
[32]King SJ, Heath PJ, Luque I, et al. Distribution and genetic diversity of suilysin in Streptococcus suis isolated from different diseases of pigs and characterization of the genetic basis of suilysin absence. Infection and immunity 2001 Dec;69(12):7572-82.
[33]Vatter H, Mursch K, Zimmermann M, et al. Endothelin-converting enzyme activity in human cerebral circulation. Neurosurgery 2002 Aug;51(2):445-51; discussion 51-2.
[34]Awano S, Ansai T, Mochizuki H, et al. Sequencing, expression and biochemical characterization of the Porphyromonas gingivalis pepO gene encoding a protein homologous to human endothelin-converting enzyme. FEBS letters 1999 Oct 22;460(1):139-44.
[35]Froeliger EH, Oetjen J, Bond JP, et al. Streptococcus parasanguis pepO encodes an endopeptidase with structure and activity similar to those of enzymes that modulate peptide receptor signaling in eukaryotic cells. Infection and immunity 1999 Oct;67(10):5206-14.
[36]Mierau I, Tan PS, Haandrikman AJ, et al. Cloning and sequencing of the gene for a lactococcal endopeptidase, an enzyme with sequence similarity to mammalian enkephalinase. Journal of bacteriology 1993 Apr;175(7):2087-96.
[37]Oetjen J, Fives-Taylor P, Froeliger E. Characterization of a streptococcal endopeptidase with homology to human endothelin-converting enzyme. Infection and immunity 2001 Jan;69(1):58-64.
[38]Rawlings ND, Barrett AJ. Evolutionary families of metallopeptidases. Methods in enzymology 1995;248:183-228.
[39]Zhang W, Lu CP. Immunoproteomics of extracellular proteins of Chinese virulent strains of Streptococcus suis type 2. Proteomics 2007 Dec;7(24):4468-76.
[40]Zhang W, Lu CP. Immunoproteomic assay of membrane-associated proteins of Streptococcus suis type 2 China vaccine strain HA9801. Zoonoses and public health 2007;54(6-7):253-9.
[41]谭臣.猪链球菌2型ECE1的致病性及6PGD蛋白的免疫原性研究.华中农业大学博士学位论文2010.
[42]Okwumabua O, Chinnapapakkagari S. Identification of the gene encoding a 38-kilodalton immunogenic and protective antigen of Streptococcus suis. Clinical and diagnostic laboratory immunology 2005 Apr;12(4):484-90.
[43]Li Y, Martinez G, Gottschalk M, et al. Identification of a surface protein of Streptococcus suis and evaluation of its immunogenic and protective capacity in pigs. Infection and immunity 2006 Jan;74(1):305-12.
[44]Li Y, Gottschalk M, Esgleas M, et al. Immunization with recombinant Sao protein confers protection against Streptococcus suis infection. Clin Vaccine Immunol 2007 Aug;14(8):937-43.
[45]Zhang A, Xie C, Chen H, et al. Identification of immunogenic cell wall-associated proteins of Streptococcus suis serotype 2. Proteomics 2008 Sep;8(17):3506-15.
[46]Geng H, Zhu L, Yuan Y, et al. Identification and characterization of novel immunogenic proteins of Streptococcus suis serotype 2. Journal of proteome research 2008 Sep;7(9):4132-42.
[47]Zhang A, Chen B, Li R, et al. Identification of a surface protective antigen, HP0197 of Streptococcus suis serotype 2. Vaccine 2009 Aug 20;27(38):5209-13.
[48]Jing HB, Yuan J, Wang J, et al. Proteome analysis of Streptococcus suis serotype 2. Proteomics 2008 Jan;8(2):333-49.
[49]Zhang A, Chen B, Mu X, et al. Identification and characterization of a novel protective antigen, Enolase of Streptococcus suis serotype 2. Vaccine 2009 Feb 25;27(9):1348-53.
[50]Daniely D, Portnoi M, Shagan M, et al. Pneumococcal 6-phosphogluconate-dehydrogenase, a putative adhesin, induces, protective immune response in mice. Clinical and experimental immunology 2006 May;144(2):254-63.
[51]Tan C, Fu S, Liu M, et al. Cloning, expression and characterization of a cell wall surface protein, 6-phosphogluconate-dehydrogenase, of Streptococcus suis serotype 2. Veterinary microbiology 2008 Aug 25; 130(3-4):363-70.
[52]Telford JL, Barocchi MA, Margarit I, et al. Pili in gram-positive pathogens. Nature reviews 2006 Jul;4(7):509-19.
[53]Gianfaldoni C, Censini S, Hilleringmann M, et al. Streptococcus pneumoniae pilus subunits protect mice against lethal challenge. Infection and immunity 2007 Feb;75(2):1059-62.
[54]Lauer P, Rinaudo CD, Soriani M, et al. Genome analysis reveals pili in Group B Streptococcus. Science (New York, NY 2005 Jul 1;309(5731):105.
[55]Garibaldi M, Rodriguez-Ortega MJ, Mandanici F, et al. Immunoprotective activities of a Streptococcus suis pilus subunit in murine models of infection. Vaccine 2010 Apr 30;28(20):3609-16.
[1]Shope RE. Swine pox. Archives of virology 1940;1(4):457-67.
[2]De Boer GF. Swinepox. Virus isolation, experimental infections and the differentiation from vaccinia virus infections. Archives of virology 1975;49(2-3):141-50.
[3]Datt NS. Comparative Studies of Pigpox and Vaccinia Viruses. Ii. Serological Relationship. Journal of comparative pathology 1964 Jan;74:70-80.
[4]Datt NS. Comparative Studies of Pigpox and Vaccinia Viruses. I. Host Range Pathogenicity. Journal of comparative pathology 1964 Jan;74:62-9.
[5]Kasza L, Bohl EH, Jones DO. Isolation and cultivation of swine pox virus in primary cell cultures of swine origin. American journal of veterinary research 1960 Mar;21:269-73.
[6]Massung RF, Moyer RW. The molecular biology of swinepox virus. II. The infectious cycle. Virology 1991 Jan;180(1):355-64.
[7]Afonso CL, Tulman ER, Lu Z, et al. The genome of swinepox virus. Journal of virology 2002 Jan;76(2):783-90.
[8]Jubb TF, Ellis TM, Peet RL, et al. Swinepox in pigs in northern Western Australia. Australian veterinary journal 1992 Apr;69(4):99.
[9]Kim UH, Mukhajonpan V, Nii S, et al. Ultrastructural study of cell cultures infected with swinepox and orf viruses. Biken journal 1977 Jun;20(2):57-67.
[10]Olufemi BE, Ayoade GO, Ikede BO, et al. Swine pox in Nigeria. The Veterinary record 1981 Sep 26;109(13):278-80.
[11]Borst GH, Kimman TG, Gielkens AL, et al. Four sporadic cases of congenital swinepox. The Veterinary record 1990 Jul 21;127(3):61-3.
[12]Paton DJ, Brown IH, Fitton J, et al. Congenital pig pox:a case report. The Veterinary record 1990 Aug 25;127(8):204.
[1]De Boer GF. Swinepox. Virus isolation, experimental infections and the differentiation from vaccinia virus infections. Archives of virology 1975;49(2-3):141-50.
[2]Massung RF, Moyer RW. The molecular biology of swinepox virus. II. The infectious cycle. Virology 1991 Jan;180(1):355-64.
[3]Datt NS. Comparative Studies of Pigpox and Vaccinia Viruses. I. Host Range Pathogenicity. Journal of comparative pathology 1964 Jan;74:62-9.
[4]Datt NS. Comparative Studies of Pigpox and Vaccinia Viruses. Ii. Serological Relationship. Journal of comparative pathology 1964 Jan;74:70-80.
[5]Shope RE. Swine pox. Archives of virology 1940;1(4):457-67.
[6]Afonso CL, Tulman ER, Lu Z, et al. The genome of swinepox virus. Journal of virology 2002 Jan;76(2):783-90.
[7]Cheville NF. Immunofluorescent and morphologic studies on swinepox. Pathologia veterinaria 1966;3(5):556-64.
[8]van der Leek ML, Feller JA, Sorensen G, et al. Evaluation of swinepox virus as a vaccine vector in pigs using an Aujeszky's disease (pseudorabies) virus gene insert coding for glycoproteins gp50 and gp63. The Veterinary record 1994 Jan 1;134(1):13-8.
[9]Barcena J, Blasco R. Recombinant swinepox virus expressing beta-galactosidase:investigation of viral host range and gene expression levels in cell culture. Virology 1998 Apr 10;243(2):396-405.
[10]Hahn J, Park SH, Song JY, et al. Construction of recombinant swinepox viruses and expression of the classical swine fever virus E2 protein. Journal of virological methods 2001 Apr;93(1-2):49-56.
[11]Winslow BJ, Cochran MD, Holzenburg A, et al. Replication and expression of a swinepox virus vector delivering feline leukemia virus Gag and Env to cell lines of swine and feline origin. Virus research 2003 Dec;98(1):1-15.
[12]Winslow BJ, Kalabat DY, Brown SM, et al. Feline B7.1 and B7.2 proteins produced from swinepox virus vectors are natively processed and biologically active:potential for use as nonchemical adjuvants. Veterinary microbiology 2005 Nov 30;111(1-2):1-13.
[13]Bertholet C, Drillien R, Wittek R. One hundred base pairs of 51 flanking sequence of a vaccinia virus late gene are sufficient to temporally regulate late transcription. Proceedings of the National Academy of Sciences of the United States of America 1985 Apr;82(7):2096-100.
[14]Davison AJ, Moss B. Structure of vaccinia virus late promoters. Journal of molecular biology 1989 Dec 20;210(4):771-84.
[15]Mackett M, Smith GL, Moss B. General method for production and selection of infectious vaccinia virus recombinants expressing foreign genes. Journal of virology 1984 Mar;49(3):857-64.
[16]Chakrabarti S, Brechling K, Moss B. Vaccinia virus expression vector:coexpression of beta-galactosidase provides visual screening of recombinant virus plaques. Molecular and cellular biology 1985 Dec;5(12):3403-9.
[17]Panicali D, Grzelecki A, Huang C. Vaccinia virus vectors utilizing the beta-galactosidase assay for rapid selection of recombinant viruses and measurement of gene expression. Gene 1986;47(2-3):193-9.
[18]Spehner D, Drillien R, Lecocq JP. Construction of fowlpox virus vectors with intergenic insertions: expression of the beta-galactosidase gene and the measles virus fusion gene. Journal of virology 1990 Feb;64(2):527-33.
[19]Wang YF, Sun YK, Tian ZC, et al. Protection of chickens against infectious bronchitis by a recombinant fowlpox virus co-expressing IBV-S1 and chicken IFNgamma. Vaccine 2009 Nov 23;27(50):7046-52.
[20]王芳,刘胜旺,邵昱昊,et al.表达LacZ基因的重组山羊痘病毒的构建及其生物学特征研究.中国预防兽医学报2007(9)：655-60.
[21]Franke CA, Rice CM, Strauss JH, et al. Neomycin resistance as a dominant selectable marker for selection and isolation of vaccinia virus recombinants. Molecular and cellular biology 1985 Aug;5(8):1918-24.
[22]Boyle DB, Coupar BE. A dominant selectable marker for the construction of recombinant poxviruses. Gene 1988 May 15;65(1):123-8.
[23]Falkner FG, Moss B. Escherichia coli gpt gene provides dominant selection for vaccinia virus open reading frame expression vectors. Journal of virology 1988 Jun;62(6):1849-54.
[24]王艳丽,李俊辉,姜永萍,et al.以Gpt和gfp为双重筛选标记的禽痘病毒转移载体的构建及鉴定.中国预防兽医学报2009；31(7)：501-4.
[25]Dominguez J, Lorenzo MM, Blasco R. Green fluorescent protein expressed by a recombinant vaccinia virus permits early detection of infected cells by flow cytometry. Journal of immunological methods 1998 Nov 1;220(1-2):115-21.
[26]Wong YC, Lin LC, Melo-Silva CR, et al. Engineering recombinant poxviruses using a compact GFP-blasticidin resistance fusion gene for selection. Journal of virological methods 2010 Nov 10.
[27]郑敏,刘棋,金宁一,et al.山羊痘病毒Orf8-Orf18缺失重组毒株的构建和鉴定.畜牧兽医学报；2010(1)：65-70.
[28]Hanggi M, Bannwarth W, Stunnenberg HG. Conserved TAAAT motif in vaccinia virus late promoters:overlapping TATA box and site of transcription initiation. The EMBO journal 1986 May;5(5):1071-6.
[1]Cheville NF. Immunofluorescent and morphologic studies on swinepox. Pathologia veterinaria 1966;3(5):556-64.
[2]Shope RE. Swine pox. Archives of virology 1940; 1 (4):457-67.
[3]Datt NS. Comparative Studies of Pigpox and Vaccinia Viruses. I. Host Range Pathogenicity. Journal of comparative pathology 1964 Jan;74:62-9.
[4]Foley PL, Paul PS, Levings RL, et al. Swinepox virus as a vector for the delivery of immunogens. Annals of the New York Academy of Sciences 1991 Dec 27;646:220-2.
[5]Tripathy DN. Swinepox virus as a vaccine vector for swine pathogens. Advances in veterinary medicine 1999;41:463-80.
[6]Williams PP, Hall MR, McFarland MD. Immunological responses of cross-bred and in-bred miniature pigs to swine poxvirus. Veterinary immunology and immunopathology 1989 Nov 30;23(1-2):149-59.
[7]Garg SK, Meyer RC. Adaptation of swinepox virus to an established cell line. Applied microbiology 1972 Jan;23(1):180-2.
[8]Barcena J, Blasco R. Recombinant swinepox virus expressing beta-galactosidase:investigation of viral host range and gene expression levels in cell culture. Virology 1998 Apr 10;243(2):396-405.
[9]Hahn J, Park SH, Song JY, et al. Construction of recombinant swinepox viruses and expression of the classical swine fever virus E2 protein. Journal of virological methods 2001 Apr;93(1-2):49-56.
[10]Winslow BJ, Cochran MD, Holzenburg A, et al. Replication and expression of a swinepox virus vector delivering feline leukemia virus Gag and Env to cell lines of swine and feline origin. Virus research 2003 Dec;98(1):1-15.
[11]Tuboly T, Nagy E, Derbyshire JB. Potential viral vectors for the stimulation of mucosal antibody responses against enteric viral antigens in pigs. Research in veterinary science 1993 May;54(3):345-50.
[12]van der Leek ML, Feller JA, Sorensen G, et al. Evaluation of swinepox virus as a vaccine vector in pigs using an Aujeszky's disease (pseudorabies) virus gene insert coding for glycoproteins gp50 and gp63. The Veterinary record 1994 Jan 1;134(1):13-8.
[13]Winslow BJ, Kalabat DY, Brown SM, et al. Feline B7.1 and B7.2 proteins produced from swinepox virus vectors are natively processed and biologically active:potential for use as nonchemical adjuvants. Veterinary microbiology 2005 Nov 30; 111 (1-2):1-13.
[14]Wallace DB, Weyer J, Nel LH, et al. Improved method for the generation and selection of homogeneous lumpy skin disease virus (SA-Neethling) recombinants. Journal of virological methods 2007 Dec;146(1-2):52-60.
[15]Dominguez J, Lorenzo MM, Blasco R. Green fluorescent protein expressed by a recombinant vaccinia virus permits early detection of infected cells by flow cytometry. Journal of immunological methods 1998 Nov 1;220(1-2):115-21.
[1]De Boer GF. Swinepox. Virus isolation, experimental infections and the differentiation from vaccinia virus infections. Archives of virology 1975;49(2-3):141-50.
[2]Massung RF, Moyer RW. The molecular biology of swinepox virus. Ⅱ. The infectious cycle. Virology 1991 Jan;180(1):355-64.
[3]Datt NS. Comparative Studies of Pigpox and Vaccinia Viruses. Ⅰ. Host Range Pathogenicity. Journal of comparative pathology 1964 Jan;74:62-9.
[4]Datt NS. Comparative Studies of Pigpox and Vaccinia Viruses. Ii. Serological Relationship. Journal of comparative pathology 1964 Jan;74:70-80.
[5]Shope RE. Swine pox. Archives of virology 1940;1(4):457-67.
[6]Afonso CL, Tulman ER, Lu Z, et al. The genome of swinepox virus. Journal of virology 2002 Jan;76(2):783-90.
[7]Cheville NF. Immunofluorescent and morphologic studies on swinepox. Pathologia veterinaria 1966;3(5):556-64.
[8]Tuboly T, Nagy E, Derbyshire JB. Potential viral vectors for the stimulation of mucosal antibody responses against enteric viral antigens in pigs. Research in veterinary science 1993 May;54(3):345-50.
[9]van der Leek ML, Feller JA, Sorensen G, et al. Evaluation of swinepox virus as a vaccine vector in pigs using an Aujeszky's disease (pseudorabies) virus gene insert coding for glycoproteins gp50 and gp63. The Veterinary record 1994 Jan 1;134(1):13-8.
[10]Barcena J, Blasco R. Recombinant swinepox virus expressing beta-galactosidase:investigation of viral host range and gene expression levels in cell culture. Virology 1998 Apr 10;243(2):396-405.
[11]Tripathy DN. Swinepox virus as a vaccine vector for swine pathogens. Advances in veterinary medicine 1999;41:463-80.
[12]Hahn J, Park SH, Song JY, et al. Construction of recombinant swinepox viruses and expression of the classical swine fever virus E2 protein. Journal of virological methods 2001 Apr;93(1-2):49-56.
[13]Winslow BJ, Cochran MD, Holzenburg A, et al. Replication and expression of a swinepox virus vector delivering feline leukemia virus Gag and Env to cell lines of swine and feline origin. Virus research 2003 Dec;98(1):1-15.
[14]Winslow BJ, Kalabat DY, Brown SM, et al. Feline B7.1 and B7.2 proteins produced from swinepox virus vectors are natively processed and biologically active:potential for use as nonchemical adjuvants. Veterinary microbiology 2005 Nov 30;111(1-2):1-13.
[15]Chanter N, Jones PW, Alexander TJ. Meningitis in pigs caused by Streptococcus suis--a speculative review. Veterinary microbiology 1993 Jul;36(1-2):39-55.
[16]Staats JJ, Feder I, Okwumabua O, et al. Streptococcus suis:past and present. Veterinary research communications 1997 Aug;21(6):381-407.
[17]Gottschalk M, Segura M. The pathogenesis of the meningitis caused by Streptococcus suis:the unresolved questions. Veterinary microbiology 2000 Oct 1;76(3):259-72.
[18]陆承平,姚火春,范红结,et al.猪链球菌致病性研究及其公共卫生意义.中国预防医学杂志2006；7(4)：361-2.
[19]Gottschalk M. Streptococcus suis Infections in Humans:What is the prognosis for Western countries? (Part Ⅰ). Clinical Microbiology Newsletter 2010 Jun;32(12):89-96.
[20]Fittipaldi N, Fuller TE, Teel JF, et al. Serotype distribution and production of muramidase-released protein, extracellular factor and suilysin by field strains of Streptococcus suis isolated in the United States. Veterinary microbiology 2009 Nov 18;139(3-4):310-7.
[21]Gottschalk M. Streptococcus suis Infections in Humans:What is the prognosis for Western countries? (Part Ⅱ). Clinical Microbiology Newsletter 2010.
[22]Sriskandan S, Slater JD. Invasive disease and toxic shock due to zoonotic Streptococcus suis:an emerging infection in the East? PLoS medicine 2006 May;3(5):e187.
[23]陆承平.兽医微生物学(第四版).2007.
[24]Vecht U, Wisselink HJ, Jellema ML, et al. Identification of two proteins associated with virulence of Streptococcus suis type 2. Infection and immunity 1991 Sep;59(9):3156-62.
[25]Zhang W, Lu CP. Immunoproteomics of extracellular proteins of Chinese virulent strains of Streptococcus suis type 2. Proteomics 2007 Dec;7(24):4468-76.
[26]Smith HE, Vecht U, Gielkens AL, et al. Cloning and nucleotide sequence of the gene encoding the 136-kilodalton surface protein (muramidase-released protein) of Streptococcus suis type 2. Infection and immunity 1992 Jun;60(6):2361-7.
[27]欧瑜,陆承平.猪链球菌2型溶菌酶释放蛋白基因片段的克隆与表达.农业生物技术学报2002；10(1)：72-5.
[28]范红结,陆承平,唐家琪.猪链球菌2型mrp基因免疫功能片段的克隆、表达及动物试验.微生物学报2004；44(1)：54-7.
[29]Davison AJ, Moss B. Structure of vaccinia virus late promoters. Journal of molecular biology 1989 Dec 20;210(4):771-84.
[30]Gu H, Zhu H, Lu C. Use of in vivo-induced antigen technology (IVIAT) for the identification of Streptococcus suis serotype 2 in vivo-induced bacterial protein antigens. BMC microbiology 2009;9:201.
[31]Garibaldi M, Rodriguez-Ortega MJ, Mandanici F, et al. Immunoprotective activities of a Streptococcus suis pilus subunit in murine models of infection. Vaccine 2010 Apr 30;28(20):3609-16.
[32]Moss B. Genetically engineered poxviruses for recombinant gene expression, vaccination, and safety. Proceedings of the National Academy of Sciences of the United States of America 1996 Oct 15;93(21):11341-8.
[33]Paoletti E. Applications of pox virus vectors to vaccination:an update. Proceedings of the National Academy of Sciences of the United States of America 1996 Oct 15;93(21):11349-53.
[34]Yamanouchi K, Barrett T, Kai C. New approaches to the development of virus vaccines for veterinary use. Revue scientifique et technique (International Office of Epizootics) 1998 Dec;17(3):641-53.
[35]Bonifait L, de la Cruz Dominguez-Punaro M, Vaillancourt K, et al. The cell envelope subtilisin-like proteinase is a virulence determinant for Streptococcus suis. BMC microbiology 2010; 10:42.
[36]Esgleas M, Dominguez-Punaro Mde L, Li Y, et al. Immunization with SsEno fails to protect mice against challenge with Streptococcus suis serotype 2. FEMS microbiology letters 2009 May;294(1):82-8.
[37]Fittipaldi N, Sekizaki T, Takamatsu D, et al. D-alanylation of lipoteichoic acid contributes to the virulence of Streptococcus suis. Infection and immunity 2008 Aug;76(8):3587-94.
[1]Chanter N, Jones PW, Alexander TJ. Meningitis in pigs caused by Streptococcus suis-a speculative review. Veterinary microbiology 1993 Jul;36(1-2):39-55.
[2]Staats JJ, Feder I, Okwumabua O, et al. Streptococcus suis:past and present. Veterinary research communications 1997 Aug;21(6):381-407.
[3]Gottschalk M, Segura M. The pathogenesis of the meningitis caused by Streptococcus suis:the unresolved questions. Veterinary microbiology 2000 Oct 1;76(3):259-72.
[4]陆承平,姚火春,范红结,et al.猪链球菌致病性研究及其公共卫生意义.中国预防医学杂志2006；7(4)：361-2.
[5]Gottschalk M. Streptococcus suis Infections in Humans:What is the prognosis for Western countries? (Part Ⅰ). Clinical Microbiology Newsletter 2010 Jun;32(12):89-96.
[6]Fittipaldi N, Fuller TE, Teel JF, et al. Serotype distribution and production of muramidase-released protein, extracellular factor and suilysin by field strains of Streptococcus suis isolated in the United States. Veterinary microbiology 2009 Nov 18;139(3-4):310-7.
[7]Gottschalk M. Streptococcus suis Infections in Humans:What is the prognosis for Western countries? (Part Ⅱ). Clinical Microbiology Newsletter 2010.
[8]Sriskandan S, Slater JD. Invasive disease and toxic shock due to zoonotic Streptococcus suis:an emerging infection in the East? PLoS medicine 2006 May;3(5):e187.
[9]陆承平.兽医微生物学(第四版).2007.
[10]Tang J, Wang C, Feng Y, et al. Streptococcal toxic shock syndrome caused by Streptococcus suis serotype 2. PLoS medicine 2006 May;3(5):e151.
[11]姚火春,陈国强.猪链球菌1998分离株病原特性鉴定.南京农业大学学报1999；22(2)：67-70.
[12]Jacobs AA, Loeffen PL, van den Berg AJ, et al. Identification, purification, and characterization of a thiol-activated hemolysin (suilysin) of Streptococcus suis. Infection and immunity 1994 May;62(5):1742-8.
[13]Jacobs AA, van den Berg AJ, Loeffen PL. Protection of experimentally infected pigs by suilysin, the thiol-activated haemolysin of Streptococcus suis. The Veterinary record 1996 Sep 7;139(10):225-8.
[14]Liu L, Cheng G, Wang C, et al. Identification and experimental verification of protective antigens against Streptococcus suis serotype 2 based on genome sequence analysis. Current microbiology 2009 Jan;58(1):11-7.
[15]陈国强,陆承平,等.猪链球菌2型溶血素的提纯及其生物学特性.中国人兽共患病杂志2001；17(5)：75-7.
[16]King SJ, Heath PJ, Luque I, et al. Distribution and genetic diversity of suilysin in Streptococcus suis isolated from different diseases of pigs and characterization of the genetic basis of suilysin absence. Infection and immunity 2001 Dec;69(12):7572-82.
[17]De Boer GF. Swinepox. Virus isolation, experimental infections and the differentiation from vaccinia virus infections. Archives of virology 1975;49(2-3):141-50.
[18]Massung RF, Mover RW. The molecular biology of swinepox virus. II. The infectious cycle. Virology 1991 Jan;180(1):355-64.
[19]Datt NS. Comparative Studies of Pigpox and Vaccinia Viruses. I. Host Range Pathogenicity. Journal of comparative pathology 1964 Jan;74:62-9.
[20]Datt NS. Comparative Studies of Pigpox and Vaccinia Viruses. Ii. Serological Relationship. Journal of comparative pathology 1964 Jan;74:70-80.
[21]Shope RE. Swine pox. Archives of virology 1940;1(4):457-67.
[22]Cheville NF. Immunofluorescent and morphologic studies on swinepox. Pathologia veterinaria 1966;3(5):556-64.
[23]Bertholet C, Drillien R, Wittek R. One hundred base pairs of 5' flanking sequence of a vaccinia virus late gene are sufficient to temporally regulate late transcription. Proceedings of the National Academy of Sciences of the United States of America 1985 Apr;82(7):2096-100.
[24]Davison AJ, Moss B. Structure of vaccinia virus late promoters. Journal of molecular biology 1989 Dec 20;210(4):771-84.
[25]Gu H, Zhu H, Lu C. Use of in vivo-induced antigen technology (IVIAT) for the identification of Streptococcus suis serotype 2 in vivo-induced bacterial protein antigens. BMC microbiology 2009;9:201.
[26]Garibaldi M, Rodriguez-Ortega MJ, Mandanici F, et al. Immunoprotective activities of a Streptococcus suis pilus subunit in murine models of infection. Vaccine 2010 Apr 30;28(20):3609-16.
[27]Moss B. Genetically engineered poxviruses for recombinant gene expression, vaccination, and safety. Proceedings of the National Academy of Sciences of the United States of America 1996 Oct 15;93(21):11341-8.
[28]Paoletti E. Applications of pox virus vectors to vaccination:an update. Proceedings of the National Academy of Sciences of the United States of America 1996 Oct 15;93(21):11349-53.
[29]Yamanouchi K, Barrett T, Kai C. New approaches to the development of virus vaccines for veterinary use. Revue scientifique et technique (International Office of Epizootics) 1998 Dec; 17(3):641-53.
[30]Barcena J, Blasco R. Recombinant swinepox virus expressing beta-galactosidase:investigation of viral host range and gene expression levels in cell culture. Virology 1998 Apr 10;243(2):396-405.
[31]Xu L, Huang B, Du H, et al. Crystal structure of cytotoxin protein suilysin from Streptococcus suis. Protein & cell Jan; 1 (1):96-105.
[32]Staats JJ, Plattner BL, Stewart GC, et al. Presence of the Streptococcus suis suilysin gene and expression of MRP and EF correlates with high virulence in Streptococcus suis type 2 isolates. Veterinary microbiology 1999 Dec;70(3-4):201-11.
[33]Charland N, Nizet V, Rubens CE, et al. Streptococcus suis serotype 2 interactions with human brain microvascular endothelial cells. Infection and immunity 2000 Feb;68(2):637-43.
[34]Lalonde M, Segura M, Lacouture S, et al. Interactions between Streptococcus suis serotype 2 and different epithelial cell lines. Microbiology (Reading, England) 2000 Aug;146 (Pt 8):1913-21.
[35]Segura M, Gottschalk M. Streptococcus suis interactions with the murine macrophage cell line J774:adhesion and cytotoxicity. Infection and immunity 2002 Aug;70(8):4312-22.
[36]孙学强.马疱疹病毒1型感染性克隆及表达猪链球菌2型亚单位重组病毒的构建.2010.
[37]范红结,陆承平,唐家琪.猪链球菌2型mrp基因免疫功能片段的克隆、表达及动物试验.微生物学报2004；44(1)：54-7.
[38]Smith HE, Vecht U, Gielkens AL, et al. Cloning and nucleotide sequence of the gene encoding the 136-kilodalton surface protein (muramidase-released protein) of Streptococcus suis type 2. Infection and immunity 1992 Jun;60(6):2361-7.
[39]欧瑜,陆承平.猪链球菌2型溶菌酶释放蛋白基因片段的克隆与表达.农业生物技术学报2002；10(1)：72-5.
[1]Holden MT, Hauser H, Sanders M, et al. Rapid evolution of virulence and drug resistance in the emerging zoonotic pathogen Streptococcus suis. PloS one 2009;4(7):e6072.
[2]Jacobs AA, van den Berg AJ, Loeffen PL. Protection of experimentally infected pigs by suilysin, the thiol-activated haemolysin of Streptococcus suis. The Veterinary record 1996 Sep 7;139(10):225-8.
[3]Wisselink HJ, Vecht U, Stockhofe-Zurwieden N, et al. Protection of pigs against challenge with virulent Streptococcus suis serotype 2 strains by a muramidase-released protein and extracellular factor vaccine. The Veterinary record 2001 Apr 14;148(15):473-7.
[4]Okwumabua O, Chinnapapakkagari S. Identification of the gene encoding a 38-kilodalton immunogenic and protective antigen of Streptococcus suis. Clinical and diagnostic laboratory immunology 2005 Apr;12(4):484-90.
[5]Li Y, Gottschalk M, Esgleas M, et al. Immunization with recombinant Sao protein confers protection against Streptococcus suis infection. Clin Vaccine Immunol 2007 Aug;14(8):937-43.
[6]Feng Y, Pan X, Sun W, et al. Streptococcus suis enolase functions as a protective antigen displayed on the bacterial cell surface. The Journal of infectious diseases 2009 Nov 15;200(10):1583-92.
[7]Tan C, Liu M, Liu J, et al. Vaccination with Streptococcus suis serotype 2 recombinant 6PGD protein provides protection against S. suis infection in swine. FEMS microbiology letters 2009 Jul;296(1):78-83.
[8]Zhang A, Chen B, Li R, et al. Identification of a surface protective antigen, HP0197 of Streptococcus suis serotype 2. Vaccine 2009 Aug 20;27(38):5209-13.
[9]Garibaldi M, Rodriguez-Ortega MJ, Mandanici F, et al. Immunoprotective activities of a Streptococcus suis pilus subunit in murine models of infection. Vaccine 2010 Apr 30;28(20):3609-16.
[10]Vatter H, Mursch K, Zimmermann M, et al. Endothelin-converting enzyme activity in human cerebral circulation. Neurosurgery 2002 Aug;51(2):445-51; discussion 51-2.
[11]Awano S, Ansai T, Mochizuki H, et al. Sequencing, expression and biochemical characterization of the Porphyromonas gingivalis pepO gene encoding a protein homologous to human endothelin-converting enzyme. FEBS letters 1999 Oct 22;460(1):139-44.
[12]Froeliger EH, Oetjen J, Bond JP, et al. Streptococcus parasanguis pepO encodes an endopeptidase with structure and activity similar to those of enzymes that modulate peptide receptor signaling in eukaryotic cells. Infection and immunity 1999 Oct;67(10):5206-14.
[13]Mierau I, Tan PS, Haandrikman AJ, et al. Cloning and sequencing of the gene for a lactococcal endopeptidase, an enzyme with sequence similarity to mammalian enkephalinase. Journal of bacteriology 1993 Apr; 175(7):2087-96.
[14]Oetjen J, Fives-Taylor P, Froeliger E. Characterization of a streptococcal endopeptidase with homology to human endothelin-converting enzyme. Infection and immunity 2001 Jan;69(1):58-64.
[15]Rawlings ND, Barrett AJ. Evolutionary families of metallopeptidases. Methods in enzymology 1995;248:183-228.
[16]Zhang W, Lu CP. Immunoproteomics of extracellular proteins of Chinese virulent strains of Streptococcus suis type 2. Proteomics 2007 Dec;7(24):4468-76.
[17]Zhang W, Lu CP. Immunoproteomic assay of membrane-associated proteins of Streptococcus suis type 2 China vaccine strain HA9801. Zoonoses and public health 2007;54(6-7):253-9.
[18]谭臣.猪链球菌2型ECE1的致病性及6PGD蛋白的免疫原性研究.华中农业大学博士学位论文2010.
[19]De Boer GF. Swinepox. Virus isolation, experimental infections and the differentiation from vaccinia virus infections. Archives of virology 1975;49(2-3):141-50.
[20]Massung RF, Moyer RW. The molecular biology of swinepox virus. II. The infectious cycle. Virology 1991 Jan;180(1):355-64.
[21]Datt NS. Comparative Studies of Pigpox and Vaccinia Viruses. I. Host Range Pathogenicity. Journal of comparative pathology 1964 Jan;74:62-9.
[22]Datt NS. Comparative Studies of Pigpox and Vaccinia Viruses. Ii. Serological Relationship. Journal of comparative pathology 1964 Jan;74:70-80.
[23]Shope RE. Swine pox. Archives of virology 1940;1(4):457-67.
[24]Bertholet C, Drillien R, Wittek R. One hundred base pairs of 5' flanking sequence of a vaccinia virus late gene are sufficient to temporally regulate late transcription. Proceedings of the National Academy of Sciences of the United States of America 1985 Apr;82(7):2096-100.
[25]Davison AJ, Moss B. Structure of vaccinia virus late promoters. Journal of molecular biology 1989 Dec 20;210(4):771-84.
[26]Gu H, Zhu H, Lu C. Use of in vivo-induced antigen technology (IVIAT) for the identification of Streptococcus suis serotype 2 in vivo-induced bacterial protein antigens. BMC microbiology 2009;9:201.
[27]Chanter N, Jones PW, Alexander TJ. Meningitis in pigs caused by Streptococcus suis--a speculative review. Veterinary microbiology 1993 Jul;36(1-2):39-55.
[28]Staats JJ, Feder I, Okwumabua O, et al. Streptococcus suis:past and present. Veterinary research communications 1997 Aug;21(6):381-407.
[29]Gottschalk M, Segura M. The pathogenesis of the meningitis caused by Streptococcus suis:the unresolved questions. Veterinary microbiology 2000 Oct 1;76(3):259-72.
[30]陆承平,姚火春,范红结,et al.猪链球菌致病性研究及其公共卫生意义.中国预防医学杂志2006；7(4)：361-2.
[31]Gottschalk M. Streptococcus suis Infections in Humans:What is the prognosis for Western countries? (Part I). Clinical Microbiology Newsletter 2010 Jun;32(12):89-96.
[32]Fittipaldi N, Fuller TE, Teel JF, et al. Serotype distribution and production of muramidase-released protein, extracellular factor and suilysin by field strains of Streptococcus suis isolated in the United States. Veterinary microbiology 2009 Nov 18;139(3-4):310-7.
[33]Gottschalk M. Streptococcus suis Infections in Humans:What is the prognosis for Western countries? (Part II). Clinical Microbiology Newsletter 2010.
[34]Sriskandan S, Slater JD. Invasive disease and toxic shock due to zoonotic Streptococcus suis:an emerging infection in the East? PLoS medicine 2006 May;3(5):e187.
[2]Conroy JD, Meyer RC. Electron microscopy of swinepox virus in germfree pigs and in cell culture. American journal of veterinary research 1971 Dec;32(12):2021-32.
[3]Teppema JS, De Boer GF. Ultrastructural aspects of experimental swinepox with special reference to inclusion bodies. Archives of virology 1975;49(2-3):151-63.
[4]De Boer GF. Swinepox. Virus isolation, experimental infections and the differentiation from vaccinia virus infections. Archives of virology 1975;49(2-3):141-50.
[5]Massung RF, Moyer RW. The molecular biology of swinepox virus. Ⅱ. The infectious cycle. Virology 1991 Jan;180(1):355-64.
[6]Datt NS. Comparative Studies of Pigpox and Vaccinia Viruses. Ⅰ. Host Range Pathogenicity. Journal of comparative pathology 1964 Jan;74:62-9.
[7]Datt NS. Comparative Studies of Pigpox and Vaccinia Viruses. Ii. Serological Relationship. Journal of comparative pathology 1964 Jan;74:70-80.
[8]Shope RE. Swine pox. Archives of virology 1940; 1 (4):457-67.
[9]Afonso CL, Tulman ER, Lu Z, et al. The genome of swinepox virus. Journal of virology 2002 Jan;76(2):783-90.
[10]Schnitzlein WM, Tripathy DN. Identification and nucleotide sequence of the thymidine kinase gene of swinepox virus. Virology 1991 Apr;181(2):727-32.
[11]Kasza L, Bohl EH, Jones DO. Isolation and cultivation of swine pox virus in primary cell cultures of swine origin. American journal of veterinary research 1960 Mar;21:269-73.
[12]Delhon G, Tulman E, Afonso C, et al. Genus Suipoxvirus. Poxviruses,2007:203-15.
[13]Paton DJ, Brown IH, Fitton J, et al. Congenital pig pox:a case report. The Veterinary record 1990 Aug 25;127(8):204.
[14]Jubb TF, Ellis TM, Peet RL, et al. Swinepox in pigs in northern Western Australia. Australian veterinary journal 1992 Apr;69(4):99.
[15]Borst GH, Kimman TG, Gielkens AL, et al. Four sporadic cases of congenital swinepox. The Veterinary record 1990 Jul 21;127(3):61-3.
[16]Kim UH, Mukhajonpan V, Nii S, et al. Ultrastructural study of cell cultures infected with swinepox and orf viruses. Biken journal 1977 Jun;20(2):57-67.
[17]Olufemi BE, Ayoade GO, Ikede BO, et al. Swine pox in Nigeria. The Veterinary record 1981 Sep 26;109(13):278-80.
[18]Kasza L, Griesemer RA. Experimental swine pox. American journal of veterinary research 1962 May;23:443-51.
[19]Meyer RC, Conroy JD. Experimental swinepox in gnotobiotic piglets. Research in veterinary science 1972 Jul;13(4):334-8.
[20]Miller RB, Olson LD. Experimental induction of cutaneous streptococcal abscesses in swine as a sequela to swinepox. American journal of veterinary research 1980 Mar;41(3):341-7.
[21]Massung RF, Jayarama V, Moyer RW. DNA sequence analysis of conserved and unique regions of swinepox virus:identification of genetic elements supporting phenotypic observations including a novel G protein-coupled receptor homologue. Virology 1993 Dec; 197(2):511-28.
[22]Brunetti CR, Paulose-Murphy M, Singh R, et al. A secreted high-affinity inhibitor of human TNF from Tanapox virus. Proceedings of the National Academy of Sciences of the United States of America 2003 Apr 15;100(8):4831-6.
[23]Bartee E, Mansouri M, Hovey Nerenberg BT, et al. Downregulation of major histocompatibility complex class I by human ubiquitin ligases related to viral immune evasion proteins. Journal of virology 2004 Feb;78(3):1109-20.
[24]Sanderson CM, Parkinson JE, Hollinshead M, et al. Overexpression of the vaccinia virus A38L integral membrane protein promotes Ca2+ influx into infected cells. Journal of virology 1996 Feb;70(2):905-14.
[25]Najarro P, Lee HJ, Fox J, et al. Yaba-like disease virus protein 7L is a cell-surface receptor for chemokine CCL1. The Journal of general virology 2003 Dec;84(Pt 12):3325-36.
[26]Guerin JL, Gelfi J, Boullier S, et al. Myxoma virus leukemia-associated protein is responsible for major histocompatibility complex class I and Fas-CD95 down-regulation and defines scrapins, a new group of surface cellular receptor abductor proteins. Journal of virology 2002 Mar;76(6):2912-23.
[27]Mansouri M, Bartee E, Gouveia K, et al. The PHD/LAP-domain protein M153R of myxomavirus is a ubiquitin ligase that induces the rapid internalization and lysosomal destruction of CD4. Journal of virology 2003 Jan;77(2):1427-40.
[28]Langland JO, Jacobs BL. The role of the PKR-inhibitory genes, E3L and K3L, in determining vaccinia virus host range. Virology 2002 Jul 20;299(1):133-41.
[29]Smith GL, Chan YS, Howard ST. Nucleotide sequence of 42 kbp of vaccinia virus strain WR from near the right inverted terminal repeat. The Journal of general virology 1991 Jun;72 (Pt 6):1349-76.
[30]Bowie AG, Haga IR. The role of Toll-like receptors in the host response to viruses. Molecular immunology 2005 May;42(8):859-67.
[31]Stack J, Haga IR, Schroder M, et al. Vaccinia virus protein A46R targets multiple Toll-like-interleukin-1 receptor adaptors and contributes to virulence. The Journal of experimental medicine 2005 Mar 21;201 (6):1007-18.
[32]DiPerna G, Stack J, Bowie AG, et al. Poxvirus protein NIL targets the I-kappaB kinase complex, inhibits signaling to NF-kappaB by the tumor necrosis factor superfamily of receptors, and inhibits NF-kappaB and IRF3 signaling by toll-like receptors. The Journal of biological chemistry 2004 Aug 27;279(35):36570-8.
[33]Everett H, Barry M, Lee SF, et al. M11L:a novel mitochondria-localized protein of myxoma virus that blocks apoptosis of infected leukocytes. The Journal of experimental medicine 2000 May 1;191(9):1487-98.
[34]Perkus ME, Goebel SJ, Davis SW, et al. Vaccinia virus host range genes. Virology 1990 Nov;179(1):276-86.
[35]Betakova T, Wolffe EJ, Moss B. The vaccinia virus A14.5L gene encodes a hydrophobic 53-amino-acid virion membrane protein that enhances virulence in mice and is conserved among vertebrate poxviruses. Journal of virology 2000 May;74(9):4085-92.
[36]Senkevich TG, Koonin EV, Buller RM. A poxvirus protein with a RING zinc finger motif is of crucial importance for virulence. Virology 1994 Jan;198(1):118-28.
[37]Senkevich TG, Wolffe EJ, Buller RM. Ectromelia virus RING finger protein is localized in virus factories and is required for virus replication in macrophages. Journal of virology 1995 Jul;69(7):4103-11.
[38]Nerenberg BT, Taylor J, Bartee E, et al. The poxviral RING protein p28 is a ubiquitin ligase that targets ubiquitin to viral replication factories. Journal of virology 2005 Jan;79(1):597-601.
[39]Gillard S, Spehner D, Drillien R, et al. Localization and sequence of a vaccinia virus gene required for multiplication in human cells. Proceedings of the National Academy of Sciences of the United States of America 1986 Aug;83(15):5573-7.
[40]Mossman K, Lee SF, Barry M, et al. Disruption of M-T5, a novel myxoma virus gene member of poxvirus host range superfamily, results in dramatic attenuation of myxomatosis in infected European rabbits. Journal of virology 1996 Jul;70(7):4394-410.
[41]Spehner D, Gillard S, Drillien R, et al. A cowpox virus gene required for multiplication in Chinese hamster ovary cells. Journal of virology 1988 Apr;62(4):1297-304.
[42]Camus-Bouclainville C, Fiette L, Bouchiha S, et al. A virulence factor of myxoma virus colocalizes with NF-kappaB in the nucleus and interferes with inflammation. Journal of virology 2004 Mar;78(5):2510-6.
[43]Johnston JB, Wang G, Barrett JW, et al. Myxoma virus M-T5 protects infected cells from the stress of cell cycle arrest through its interaction with host cell cullin-1. Journal of virology 2005 Aug;79(16):10750-63.
[44]Antoine G, Scheiflinger F, Dorner F, et al. The complete genomic sequence of the modified vaccinia Ankara strain:comparison with other orthopoxviruses. Virology 1998 May 10;244(2):365-96.
[45]Shchelkunov SN, Safronov PF, Totmenin AV, et al. The genomic sequence analysis of the left and right species-specific terminal region of a cowpox virus strain reveals unique sequences and a cluster of intact ORFs for immunomodulatory and host range proteins. Virology 1998 Apr 10;243(2):432-60.
[46]Kochneva G, Kolosova I, Maksyutova T, et al. Effects of deletions of kelch-like genes on cowpox virus biological properties. Archives of virology 2005 Sep; 150(9):1857-70.
[47]Tulman ER, Afonso CL, Lu Z, et al. The genomes of sheeppox and goatpox viruses. Journal of virology 2002 Jun;76(12):6054-61.
[48]Pires de Miranda M, Reading PC, Tscharke DC, et al. The vaccinia virus kelch-like protein C2L affects calcium-independent adhesion to the extracellular matrix and inflammation in a murine intradermal model. The Journal of general virology 2003 Sep;84(Pt 9):2459-71.
[49]Mackett M, Smith GL, Moss B. General method for production and selection of infectious vaccinia virus recombinants expressing foreign genes. Journal of virology 1984 Mar;49(3):857-64.
[50]van der Leek ML, Feller JA, Sorensen G, et al. Evaluation of swinepox virus as a vaccine vector in pigs using an Aujeszky's disease (pseudorabies) virus gene insert coding for glycoproteins gp50 and gp63. The Veterinary record 1994 Jan 1;134(1):13-8.
[51]Hahn J, Park SH, Song JY, et al. Construction of recombinant swinepox viruses and expression of the classical swine fever virus E2 protein. Journal of virological methods 2001 Apr;93(1-2):49-56.
[52]Winslow BJ, Cochran MD, Holzenburg A, et al. Replication and expression of a swinepox virus vector delivering feline leukemia virus Gag and Env to cell lines of swine and feline origin. Virus research 2003 Dec;98(1):1-15.
[53]Barcena J, Blasco R. Recombinant swinepox virus expressing beta-galactosidase:investigation of viral host range and gene expression levels in cell culture. Virology 1998 Apr 10;243(2):396-405.
[54]Winslow BJ, Kalabat DY, Brown SM, et al. Feline B7.1 and B7.2 proteins produced from swinepox virus vectors are natively processed and biologically active:potential for use as nonchemical adjuvants. Veterinary microbiology 2005 Nov 30;111(1-2):1-13.
[55]Domi A, Moss B. Engineering of a vaccinia virus bacterial artificial chromosome in Escherichia coli by bacteriophage lambda-based recombination. Nature methods 2005 Feb;2(2):95-7.
[56]Moss B. Genetically engineered poxviruses for recombinant gene expression, vaccination, and safety. Proceedings of the National Academy of Sciences of the United States of America 1996 Oct 15;93(21):11341-8.
[57]Paoletti E. Applications of pox virus vectors to vaccination:an update. Proceedings of the National Academy of Sciences of the United States of America 1996 Oct 15;93(21):11349-53.
[58]Yamanouchi K, Barrett T, Kai C. New approaches to the development of virus vaccines for veterinary use. Revue scientifique et technique (International Office of Epizootics) 1998 Dec;17(3):641-53.
[1]Chanter N, Jones PW, Alexander TJ. Meningitis in pigs caused by Streptococcus suis-a speculative review. Veterinary microbiology 1993 Jul;36(1-2):39-55.
[2]Staats JJ, Feder I, Okwumabua O, et al. Streptococcus suis:past and present. Veterinary research communications 1997 Aug;21(6):381-407.
[3]Gottschalk M, Segura M. The pathogenesis of the meningitis caused by Streptococcus suis:the unresolved questions. Veterinary microbiology 2000 Oct 1;76(3):259-72.
[4]陆承平,姚火春,范红结,et al.猪链球菌致病性研究及其公共卫生意义.中国预防医学杂志2006；7(4)：361-2.
[5]Gottschalk M. Streptococcus suis Infections in Humans:What is the prognosis for Western countries? (Part Ⅰ). Clinical Microbiology Newsletter 2010 Jun;32(12):89-96.
[6]Fittipaldi N, Fuller TE, Teel JF, et al. Serotype distribution and production of muramidase-released protein, extracellular factor and suilysin by field strains of Streptococcus suis isolated in the United States. Veterinary microbiology 2009 Nov 18;139(3-4):310-7.
[7]Gottschalk M. Streptococcus suis Infections in Humans:What is the prognosis for Western countries? (Part Ⅱ). Clinical Microbiology Newsletter 2010.
[8]Sriskandan S, Slater JD. Invasive disease and toxic shock due to zoonotic Streptococcus suis:an emerging infection in the East? PLoS medicine 2006 May;3(5):e187.
[9]陆承平.兽医微生物学(第四版).2007.
[10]Tang J, Wang C, Feng Y, et al. Streptococcal toxic shock syndrome caused by Streptococcus suis serotype 2. PLoS medicine 2006 May;3(5):e151.
[11]姚火春,陈国强.猪链球菌1998分离株病原特性鉴定.南京农业大学学报1999；22(2)：67-70.
[12]Holden MT, Hauser H, Sanders M, et al. Rapid evolution of virulence and drug resistance in the emerging zoonotic pathogen Streptococcus suis. PloS one 2009;4(7):e6072.
[13]Vecht U, Wisselink HJ, Jellema ML, et al. Identification of two proteins associated with virulence of Streptococcus suis type 2. Infection and immunity 1991 Sep;59(9):3156-62.
[14]Smith HE, Vecht U, Gielkens AL, et al. Cloning and nucleotide sequence of the gene encoding the 136-kilodalton surface protein (muramidase-released protein) of Streptococcus suis type 2. Infection and immunity 1992 Jun;60(6):2361-7.
[15]曾巧英,陆承平.猪链球菌2型溶菌酶释放蛋白的黏附作用.南京农业大学学报2002；25(4)：67-71.
[16]范红结,陆承平,唐家琪.猪链球菌2型mrp基因免疫功能片段的克隆、表达及动物试验.微生物学报2004；44(1)：54-7.
[17]范红结,陆承平,唐家琪.马链球菌兽疫亚种类M基因和猪链球菌2型mrp基因片段的融合表达及仔猪免疫试验.南京农业大学学报2003；26(4)：78-81.
[18]Smith HE, Reek FH, Vecht U, et al. Repeats in an extracellular protein of weakly pathogenic strains of Streptococcus suis type 2 are absent in pathogenic strains. Infection and immunity 1993 Aug;61(8):3318-26.
[19]Wisselink HJ, Vecht U, Stockhofe-Zurwieden N, et al. Protection of pigs against challenge with virulent Streptococcus suis serotype 2 strains by a muramidase-released protein and extracellular factor vaccine. The Veterinary record 2001 Apr 14;148(15):473-7.
[20]Jacobs AA, Loeffen PL, van den Berg AJ, et al. Identification, purification, and characterization of a thiol-activated hemolysin (suilysin) of Streptococcus suis. Infection and immunity 1994 May;62(5):1742-8.
[21]Gottschalk MG, Lacouture S, Dubreuil JD. Characterization of Streptococcus suis capsular type 2 haemolysin. Microbiology (Reading, England) 1995 Jan;141 (Pt 1):189-95.
[22]陈国强,姚火春.猪链球菌2型溶血毒素的产生条件及其特性分析.南京农业大学学报2000；23(3)：71-5.
[23]Staats JJ, Plattner BL, Stewart GC, et al. Presence of the Streptococcus suis suilysin gene and expression of MRP and EF correlates with high virulence in Streptococcus suis type 2 isolates. Veterinary microbiology 1999 Dec;70(3-4):201-11.
[24]Charland N, Nizet V, Rubens CE, et al. Streptococcus suis serotype 2 interactions with human brain microvascular endothelial cells. Infection and immunity 2000 Feb;68(2):637-43.
[25]Lalonde M, Segura M, Lacouture S, et al. Interactions between Streptococcus suis serotype 2 and different epithelial cell lines. Microbiology (Reading, England) 2000 Aug;146 (Pt 8):1913-21.
[26]Segura M, Gottschalk M. Streptococcus suis interactions with the murine macrophage cell line J774: adhesion and cytotoxicity. Infection and immunity 2002 Aug;70(8):4312-22.
[27]Norton PM, Rolph C, Ward PN, et al. Epithelial invasion and cell lysis by virulent strains of Streptococcus suis is enhanced by the presence of suilysin. FEMS immunology and medical microbiology 1999 Oct;26(1):25-35.
[28]Allen AG, Bolitho S, Lindsay H, et al. Generation and characterization of a defined mutant of Streptococcus suis lacking suilysin. Infection and immunity 2001 Apr;69(4):2732-5.
[29]Jacobs AA, van den Berg AJ, Loeffen PL. Protection of experimentally infected pigs by suilysin, the thiol-activated haemolysin of Streptococcus suis. The Veterinary record 1996 Sep 7;139(10):225-8.
[30]Liu L, Cheng G, Wang C, et al. Identification and experimental verification of protective antigens against Streptococcus suis serotype 2 based on genome sequence analysis. Current microbiology 2009 Jan;58(1):11-7.
[31]陈国强,陆承平,等.猪链球菌2型溶血素的提纯及其生物学特性.中国人兽共患病杂志2001；17(5)：75-7.
[32]King SJ, Heath PJ, Luque I, et al. Distribution and genetic diversity of suilysin in Streptococcus suis isolated from different diseases of pigs and characterization of the genetic basis of suilysin absence. Infection and immunity 2001 Dec;69(12):7572-82.
[33]Vatter H, Mursch K, Zimmermann M, et al. Endothelin-converting enzyme activity in human cerebral circulation. Neurosurgery 2002 Aug;51(2):445-51; discussion 51-2.
[34]Awano S, Ansai T, Mochizuki H, et al. Sequencing, expression and biochemical characterization of the Porphyromonas gingivalis pepO gene encoding a protein homologous to human endothelin-converting enzyme. FEBS letters 1999 Oct 22;460(1):139-44.
[35]Froeliger EH, Oetjen J, Bond JP, et al. Streptococcus parasanguis pepO encodes an endopeptidase with structure and activity similar to those of enzymes that modulate peptide receptor signaling in eukaryotic cells. Infection and immunity 1999 Oct;67(10):5206-14.
[36]Mierau I, Tan PS, Haandrikman AJ, et al. Cloning and sequencing of the gene for a lactococcal endopeptidase, an enzyme with sequence similarity to mammalian enkephalinase. Journal of bacteriology 1993 Apr;175(7):2087-96.
[37]Oetjen J, Fives-Taylor P, Froeliger E. Characterization of a streptococcal endopeptidase with homology to human endothelin-converting enzyme. Infection and immunity 2001 Jan;69(1):58-64.
[38]Rawlings ND, Barrett AJ. Evolutionary families of metallopeptidases. Methods in enzymology 1995;248:183-228.
[39]Zhang W, Lu CP. Immunoproteomics of extracellular proteins of Chinese virulent strains of Streptococcus suis type 2. Proteomics 2007 Dec;7(24):4468-76.
[40]Zhang W, Lu CP. Immunoproteomic assay of membrane-associated proteins of Streptococcus suis type 2 China vaccine strain HA9801. Zoonoses and public health 2007;54(6-7):253-9.
[41]谭臣.猪链球菌2型ECE1的致病性及6PGD蛋白的免疫原性研究.华中农业大学博士学位论文2010.
[42]Okwumabua O, Chinnapapakkagari S. Identification of the gene encoding a 38-kilodalton immunogenic and protective antigen of Streptococcus suis. Clinical and diagnostic laboratory immunology 2005 Apr;12(4):484-90.
[43]Li Y, Martinez G, Gottschalk M, et al. Identification of a surface protein of Streptococcus suis and evaluation of its immunogenic and protective capacity in pigs. Infection and immunity 2006 Jan;74(1):305-12.
[44]Li Y, Gottschalk M, Esgleas M, et al. Immunization with recombinant Sao protein confers protection against Streptococcus suis infection. Clin Vaccine Immunol 2007 Aug;14(8):937-43.
[45]Zhang A, Xie C, Chen H, et al. Identification of immunogenic cell wall-associated proteins of Streptococcus suis serotype 2. Proteomics 2008 Sep;8(17):3506-15.
[46]Geng H, Zhu L, Yuan Y, et al. Identification and characterization of novel immunogenic proteins of Streptococcus suis serotype 2. Journal of proteome research 2008 Sep;7(9):4132-42.
[47]Zhang A, Chen B, Li R, et al. Identification of a surface protective antigen, HP0197 of Streptococcus suis serotype 2. Vaccine 2009 Aug 20;27(38):5209-13.
[48]Jing HB, Yuan J, Wang J, et al. Proteome analysis of Streptococcus suis serotype 2. Proteomics 2008 Jan;8(2):333-49.
[49]Zhang A, Chen B, Mu X, et al. Identification and characterization of a novel protective antigen, Enolase of Streptococcus suis serotype 2. Vaccine 2009 Feb 25;27(9):1348-53.
[50]Daniely D, Portnoi M, Shagan M, et al. Pneumococcal 6-phosphogluconate-dehydrogenase, a putative adhesin, induces, protective immune response in mice. Clinical and experimental immunology 2006 May;144(2):254-63.
[51]Tan C, Fu S, Liu M, et al. Cloning, expression and characterization of a cell wall surface protein, 6-phosphogluconate-dehydrogenase, of Streptococcus suis serotype 2. Veterinary microbiology 2008 Aug 25; 130(3-4):363-70.
[52]Telford JL, Barocchi MA, Margarit I, et al. Pili in gram-positive pathogens. Nature reviews 2006 Jul;4(7):509-19.
[53]Gianfaldoni C, Censini S, Hilleringmann M, et al. Streptococcus pneumoniae pilus subunits protect mice against lethal challenge. Infection and immunity 2007 Feb;75(2):1059-62.
[54]Lauer P, Rinaudo CD, Soriani M, et al. Genome analysis reveals pili in Group B Streptococcus. Science (New York, NY 2005 Jul 1;309(5731):105.
[55]Garibaldi M, Rodriguez-Ortega MJ, Mandanici F, et al. Immunoprotective activities of a Streptococcus suis pilus subunit in murine models of infection. Vaccine 2010 Apr 30;28(20):3609-16.
[1]Shope RE. Swine pox. Archives of virology 1940;1(4):457-67.
[2]De Boer GF. Swinepox. Virus isolation, experimental infections and the differentiation from vaccinia virus infections. Archives of virology 1975;49(2-3):141-50.
[3]Datt NS. Comparative Studies of Pigpox and Vaccinia Viruses. Ii. Serological Relationship. Journal of comparative pathology 1964 Jan;74:70-80.
[4]Datt NS. Comparative Studies of Pigpox and Vaccinia Viruses. I. Host Range Pathogenicity. Journal of comparative pathology 1964 Jan;74:62-9.
[5]Kasza L, Bohl EH, Jones DO. Isolation and cultivation of swine pox virus in primary cell cultures of swine origin. American journal of veterinary research 1960 Mar;21:269-73.
[6]Massung RF, Moyer RW. The molecular biology of swinepox virus. II. The infectious cycle. Virology 1991 Jan;180(1):355-64.
[7]Afonso CL, Tulman ER, Lu Z, et al. The genome of swinepox virus. Journal of virology 2002 Jan;76(2):783-90.
[8]Jubb TF, Ellis TM, Peet RL, et al. Swinepox in pigs in northern Western Australia. Australian veterinary journal 1992 Apr;69(4):99.
[9]Kim UH, Mukhajonpan V, Nii S, et al. Ultrastructural study of cell cultures infected with swinepox and orf viruses. Biken journal 1977 Jun;20(2):57-67.
[10]Olufemi BE, Ayoade GO, Ikede BO, et al. Swine pox in Nigeria. The Veterinary record 1981 Sep 26;109(13):278-80.
[11]Borst GH, Kimman TG, Gielkens AL, et al. Four sporadic cases of congenital swinepox. The Veterinary record 1990 Jul 21;127(3):61-3.
[12]Paton DJ, Brown IH, Fitton J, et al. Congenital pig pox:a case report. The Veterinary record 1990 Aug 25;127(8):204.
[1]De Boer GF. Swinepox. Virus isolation, experimental infections and the differentiation from vaccinia virus infections. Archives of virology 1975;49(2-3):141-50.
[2]Massung RF, Moyer RW. The molecular biology of swinepox virus. II. The infectious cycle. Virology 1991 Jan;180(1):355-64.
[3]Datt NS. Comparative Studies of Pigpox and Vaccinia Viruses. I. Host Range Pathogenicity. Journal of comparative pathology 1964 Jan;74:62-9.
[4]Datt NS. Comparative Studies of Pigpox and Vaccinia Viruses. Ii. Serological Relationship. Journal of comparative pathology 1964 Jan;74:70-80.
[5]Shope RE. Swine pox. Archives of virology 1940;1(4):457-67.
[6]Afonso CL, Tulman ER, Lu Z, et al. The genome of swinepox virus. Journal of virology 2002 Jan;76(2):783-90.
[7]Cheville NF. Immunofluorescent and morphologic studies on swinepox. Pathologia veterinaria 1966;3(5):556-64.
[8]van der Leek ML, Feller JA, Sorensen G, et al. Evaluation of swinepox virus as a vaccine vector in pigs using an Aujeszky's disease (pseudorabies) virus gene insert coding for glycoproteins gp50 and gp63. The Veterinary record 1994 Jan 1;134(1):13-8.
[9]Barcena J, Blasco R. Recombinant swinepox virus expressing beta-galactosidase:investigation of viral host range and gene expression levels in cell culture. Virology 1998 Apr 10;243(2):396-405.
[10]Hahn J, Park SH, Song JY, et al. Construction of recombinant swinepox viruses and expression of the classical swine fever virus E2 protein. Journal of virological methods 2001 Apr;93(1-2):49-56.
[11]Winslow BJ, Cochran MD, Holzenburg A, et al. Replication and expression of a swinepox virus vector delivering feline leukemia virus Gag and Env to cell lines of swine and feline origin. Virus research 2003 Dec;98(1):1-15.
[12]Winslow BJ, Kalabat DY, Brown SM, et al. Feline B7.1 and B7.2 proteins produced from swinepox virus vectors are natively processed and biologically active:potential for use as nonchemical adjuvants. Veterinary microbiology 2005 Nov 30;111(1-2):1-13.
[13]Bertholet C, Drillien R, Wittek R. One hundred base pairs of 51 flanking sequence of a vaccinia virus late gene are sufficient to temporally regulate late transcription. Proceedings of the National Academy of Sciences of the United States of America 1985 Apr;82(7):2096-100.
[14]Davison AJ, Moss B. Structure of vaccinia virus late promoters. Journal of molecular biology 1989 Dec 20;210(4):771-84.
[15]Mackett M, Smith GL, Moss B. General method for production and selection of infectious vaccinia virus recombinants expressing foreign genes. Journal of virology 1984 Mar;49(3):857-64.
[16]Chakrabarti S, Brechling K, Moss B. Vaccinia virus expression vector:coexpression of beta-galactosidase provides visual screening of recombinant virus plaques. Molecular and cellular biology 1985 Dec;5(12):3403-9.
[17]Panicali D, Grzelecki A, Huang C. Vaccinia virus vectors utilizing the beta-galactosidase assay for rapid selection of recombinant viruses and measurement of gene expression. Gene 1986;47(2-3):193-9.
[18]Spehner D, Drillien R, Lecocq JP. Construction of fowlpox virus vectors with intergenic insertions: expression of the beta-galactosidase gene and the measles virus fusion gene. Journal of virology 1990 Feb;64(2):527-33.
[19]Wang YF, Sun YK, Tian ZC, et al. Protection of chickens against infectious bronchitis by a recombinant fowlpox virus co-expressing IBV-S1 and chicken IFNgamma. Vaccine 2009 Nov 23;27(50):7046-52.
[20]王芳,刘胜旺,邵昱昊,et al.表达LacZ基因的重组山羊痘病毒的构建及其生物学特征研究.中国预防兽医学报2007(9)：655-60.
[21]Franke CA, Rice CM, Strauss JH, et al. Neomycin resistance as a dominant selectable marker for selection and isolation of vaccinia virus recombinants. Molecular and cellular biology 1985 Aug;5(8):1918-24.
[22]Boyle DB, Coupar BE. A dominant selectable marker for the construction of recombinant poxviruses. Gene 1988 May 15;65(1):123-8.
[23]Falkner FG, Moss B. Escherichia coli gpt gene provides dominant selection for vaccinia virus open reading frame expression vectors. Journal of virology 1988 Jun;62(6):1849-54.
[24]王艳丽,李俊辉,姜永萍,et al.以Gpt和gfp为双重筛选标记的禽痘病毒转移载体的构建及鉴定.中国预防兽医学报2009；31(7)：501-4.
[25]Dominguez J, Lorenzo MM, Blasco R. Green fluorescent protein expressed by a recombinant vaccinia virus permits early detection of infected cells by flow cytometry. Journal of immunological methods 1998 Nov 1;220(1-2):115-21.
[26]Wong YC, Lin LC, Melo-Silva CR, et al. Engineering recombinant poxviruses using a compact GFP-blasticidin resistance fusion gene for selection. Journal of virological methods 2010 Nov 10.
[27]郑敏,刘棋,金宁一,et al.山羊痘病毒Orf8-Orf18缺失重组毒株的构建和鉴定.畜牧兽医学报；2010(1)：65-70.
[28]Hanggi M, Bannwarth W, Stunnenberg HG. Conserved TAAAT motif in vaccinia virus late promoters:overlapping TATA box and site of transcription initiation. The EMBO journal 1986 May;5(5):1071-6.
[1]Cheville NF. Immunofluorescent and morphologic studies on swinepox. Pathologia veterinaria 1966;3(5):556-64.
[2]Shope RE. Swine pox. Archives of virology 1940; 1 (4):457-67.
[3]Datt NS. Comparative Studies of Pigpox and Vaccinia Viruses. I. Host Range Pathogenicity. Journal of comparative pathology 1964 Jan;74:62-9.
[4]Foley PL, Paul PS, Levings RL, et al. Swinepox virus as a vector for the delivery of immunogens. Annals of the New York Academy of Sciences 1991 Dec 27;646:220-2.
[5]Tripathy DN. Swinepox virus as a vaccine vector for swine pathogens. Advances in veterinary medicine 1999;41:463-80.
[6]Williams PP, Hall MR, McFarland MD. Immunological responses of cross-bred and in-bred miniature pigs to swine poxvirus. Veterinary immunology and immunopathology 1989 Nov 30;23(1-2):149-59.
[7]Garg SK, Meyer RC. Adaptation of swinepox virus to an established cell line. Applied microbiology 1972 Jan;23(1):180-2.
[8]Barcena J, Blasco R. Recombinant swinepox virus expressing beta-galactosidase:investigation of viral host range and gene expression levels in cell culture. Virology 1998 Apr 10;243(2):396-405.
[9]Hahn J, Park SH, Song JY, et al. Construction of recombinant swinepox viruses and expression of the classical swine fever virus E2 protein. Journal of virological methods 2001 Apr;93(1-2):49-56.
[10]Winslow BJ, Cochran MD, Holzenburg A, et al. Replication and expression of a swinepox virus vector delivering feline leukemia virus Gag and Env to cell lines of swine and feline origin. Virus research 2003 Dec;98(1):1-15.
[11]Tuboly T, Nagy E, Derbyshire JB. Potential viral vectors for the stimulation of mucosal antibody responses against enteric viral antigens in pigs. Research in veterinary science 1993 May;54(3):345-50.
[12]van der Leek ML, Feller JA, Sorensen G, et al. Evaluation of swinepox virus as a vaccine vector in pigs using an Aujeszky's disease (pseudorabies) virus gene insert coding for glycoproteins gp50 and gp63. The Veterinary record 1994 Jan 1;134(1):13-8.
[13]Winslow BJ, Kalabat DY, Brown SM, et al. Feline B7.1 and B7.2 proteins produced from swinepox virus vectors are natively processed and biologically active:potential for use as nonchemical adjuvants. Veterinary microbiology 2005 Nov 30; 111 (1-2):1-13.
[14]Wallace DB, Weyer J, Nel LH, et al. Improved method for the generation and selection of homogeneous lumpy skin disease virus (SA-Neethling) recombinants. Journal of virological methods 2007 Dec;146(1-2):52-60.
[15]Dominguez J, Lorenzo MM, Blasco R. Green fluorescent protein expressed by a recombinant vaccinia virus permits early detection of infected cells by flow cytometry. Journal of immunological methods 1998 Nov 1;220(1-2):115-21.
[1]De Boer GF. Swinepox. Virus isolation, experimental infections and the differentiation from vaccinia virus infections. Archives of virology 1975;49(2-3):141-50.
[2]Massung RF, Moyer RW. The molecular biology of swinepox virus. Ⅱ. The infectious cycle. Virology 1991 Jan;180(1):355-64.
[3]Datt NS. Comparative Studies of Pigpox and Vaccinia Viruses. Ⅰ. Host Range Pathogenicity. Journal of comparative pathology 1964 Jan;74:62-9.
[4]Datt NS. Comparative Studies of Pigpox and Vaccinia Viruses. Ii. Serological Relationship. Journal of comparative pathology 1964 Jan;74:70-80.
[5]Shope RE. Swine pox. Archives of virology 1940;1(4):457-67.
[6]Afonso CL, Tulman ER, Lu Z, et al. The genome of swinepox virus. Journal of virology 2002 Jan;76(2):783-90.
[7]Cheville NF. Immunofluorescent and morphologic studies on swinepox. Pathologia veterinaria 1966;3(5):556-64.
[8]Tuboly T, Nagy E, Derbyshire JB. Potential viral vectors for the stimulation of mucosal antibody responses against enteric viral antigens in pigs. Research in veterinary science 1993 May;54(3):345-50.
[9]van der Leek ML, Feller JA, Sorensen G, et al. Evaluation of swinepox virus as a vaccine vector in pigs using an Aujeszky's disease (pseudorabies) virus gene insert coding for glycoproteins gp50 and gp63. The Veterinary record 1994 Jan 1;134(1):13-8.
[10]Barcena J, Blasco R. Recombinant swinepox virus expressing beta-galactosidase:investigation of viral host range and gene expression levels in cell culture. Virology 1998 Apr 10;243(2):396-405.
[11]Tripathy DN. Swinepox virus as a vaccine vector for swine pathogens. Advances in veterinary medicine 1999;41:463-80.
[12]Hahn J, Park SH, Song JY, et al. Construction of recombinant swinepox viruses and expression of the classical swine fever virus E2 protein. Journal of virological methods 2001 Apr;93(1-2):49-56.
[13]Winslow BJ, Cochran MD, Holzenburg A, et al. Replication and expression of a swinepox virus vector delivering feline leukemia virus Gag and Env to cell lines of swine and feline origin. Virus research 2003 Dec;98(1):1-15.
[14]Winslow BJ, Kalabat DY, Brown SM, et al. Feline B7.1 and B7.2 proteins produced from swinepox virus vectors are natively processed and biologically active:potential for use as nonchemical adjuvants. Veterinary microbiology 2005 Nov 30;111(1-2):1-13.
[15]Chanter N, Jones PW, Alexander TJ. Meningitis in pigs caused by Streptococcus suis--a speculative review. Veterinary microbiology 1993 Jul;36(1-2):39-55.
[16]Staats JJ, Feder I, Okwumabua O, et al. Streptococcus suis:past and present. Veterinary research communications 1997 Aug;21(6):381-407.
[17]Gottschalk M, Segura M. The pathogenesis of the meningitis caused by Streptococcus suis:the unresolved questions. Veterinary microbiology 2000 Oct 1;76(3):259-72.
[18]陆承平,姚火春,范红结,et al.猪链球菌致病性研究及其公共卫生意义.中国预防医学杂志2006；7(4)：361-2.
[19]Gottschalk M. Streptococcus suis Infections in Humans:What is the prognosis for Western countries? (Part Ⅰ). Clinical Microbiology Newsletter 2010 Jun;32(12):89-96.
[20]Fittipaldi N, Fuller TE, Teel JF, et al. Serotype distribution and production of muramidase-released protein, extracellular factor and suilysin by field strains of Streptococcus suis isolated in the United States. Veterinary microbiology 2009 Nov 18;139(3-4):310-7.
[21]Gottschalk M. Streptococcus suis Infections in Humans:What is the prognosis for Western countries? (Part Ⅱ). Clinical Microbiology Newsletter 2010.
[22]Sriskandan S, Slater JD. Invasive disease and toxic shock due to zoonotic Streptococcus suis:an emerging infection in the East? PLoS medicine 2006 May;3(5):e187.
[23]陆承平.兽医微生物学(第四版).2007.
[24]Vecht U, Wisselink HJ, Jellema ML, et al. Identification of two proteins associated with virulence of Streptococcus suis type 2. Infection and immunity 1991 Sep;59(9):3156-62.
[25]Zhang W, Lu CP. Immunoproteomics of extracellular proteins of Chinese virulent strains of Streptococcus suis type 2. Proteomics 2007 Dec;7(24):4468-76.
[26]Smith HE, Vecht U, Gielkens AL, et al. Cloning and nucleotide sequence of the gene encoding the 136-kilodalton surface protein (muramidase-released protein) of Streptococcus suis type 2. Infection and immunity 1992 Jun;60(6):2361-7.
[27]欧瑜,陆承平.猪链球菌2型溶菌酶释放蛋白基因片段的克隆与表达.农业生物技术学报2002；10(1)：72-5.
[28]范红结,陆承平,唐家琪.猪链球菌2型mrp基因免疫功能片段的克隆、表达及动物试验.微生物学报2004；44(1)：54-7.
[29]Davison AJ, Moss B. Structure of vaccinia virus late promoters. Journal of molecular biology 1989 Dec 20;210(4):771-84.
[30]Gu H, Zhu H, Lu C. Use of in vivo-induced antigen technology (IVIAT) for the identification of Streptococcus suis serotype 2 in vivo-induced bacterial protein antigens. BMC microbiology 2009;9:201.
[31]Garibaldi M, Rodriguez-Ortega MJ, Mandanici F, et al. Immunoprotective activities of a Streptococcus suis pilus subunit in murine models of infection. Vaccine 2010 Apr 30;28(20):3609-16.
[32]Moss B. Genetically engineered poxviruses for recombinant gene expression, vaccination, and safety. Proceedings of the National Academy of Sciences of the United States of America 1996 Oct 15;93(21):11341-8.
[33]Paoletti E. Applications of pox virus vectors to vaccination:an update. Proceedings of the National Academy of Sciences of the United States of America 1996 Oct 15;93(21):11349-53.
[34]Yamanouchi K, Barrett T, Kai C. New approaches to the development of virus vaccines for veterinary use. Revue scientifique et technique (International Office of Epizootics) 1998 Dec;17(3):641-53.
[35]Bonifait L, de la Cruz Dominguez-Punaro M, Vaillancourt K, et al. The cell envelope subtilisin-like proteinase is a virulence determinant for Streptococcus suis. BMC microbiology 2010; 10:42.
[36]Esgleas M, Dominguez-Punaro Mde L, Li Y, et al. Immunization with SsEno fails to protect mice against challenge with Streptococcus suis serotype 2. FEMS microbiology letters 2009 May;294(1):82-8.
[37]Fittipaldi N, Sekizaki T, Takamatsu D, et al. D-alanylation of lipoteichoic acid contributes to the virulence of Streptococcus suis. Infection and immunity 2008 Aug;76(8):3587-94.
[1]Chanter N, Jones PW, Alexander TJ. Meningitis in pigs caused by Streptococcus suis-a speculative review. Veterinary microbiology 1993 Jul;36(1-2):39-55.
[2]Staats JJ, Feder I, Okwumabua O, et al. Streptococcus suis:past and present. Veterinary research communications 1997 Aug;21(6):381-407.
[3]Gottschalk M, Segura M. The pathogenesis of the meningitis caused by Streptococcus suis:the unresolved questions. Veterinary microbiology 2000 Oct 1;76(3):259-72.
[4]陆承平,姚火春,范红结,et al.猪链球菌致病性研究及其公共卫生意义.中国预防医学杂志2006；7(4)：361-2.
[5]Gottschalk M. Streptococcus suis Infections in Humans:What is the prognosis for Western countries? (Part Ⅰ). Clinical Microbiology Newsletter 2010 Jun;32(12):89-96.
[6]Fittipaldi N, Fuller TE, Teel JF, et al. Serotype distribution and production of muramidase-released protein, extracellular factor and suilysin by field strains of Streptococcus suis isolated in the United States. Veterinary microbiology 2009 Nov 18;139(3-4):310-7.
[7]Gottschalk M. Streptococcus suis Infections in Humans:What is the prognosis for Western countries? (Part Ⅱ). Clinical Microbiology Newsletter 2010.
[8]Sriskandan S, Slater JD. Invasive disease and toxic shock due to zoonotic Streptococcus suis:an emerging infection in the East? PLoS medicine 2006 May;3(5):e187.
[9]陆承平.兽医微生物学(第四版).2007.
[10]Tang J, Wang C, Feng Y, et al. Streptococcal toxic shock syndrome caused by Streptococcus suis serotype 2. PLoS medicine 2006 May;3(5):e151.
[11]姚火春,陈国强.猪链球菌1998分离株病原特性鉴定.南京农业大学学报1999；22(2)：67-70.
[12]Jacobs AA, Loeffen PL, van den Berg AJ, et al. Identification, purification, and characterization of a thiol-activated hemolysin (suilysin) of Streptococcus suis. Infection and immunity 1994 May;62(5):1742-8.
[13]Jacobs AA, van den Berg AJ, Loeffen PL. Protection of experimentally infected pigs by suilysin, the thiol-activated haemolysin of Streptococcus suis. The Veterinary record 1996 Sep 7;139(10):225-8.
[14]Liu L, Cheng G, Wang C, et al. Identification and experimental verification of protective antigens against Streptococcus suis serotype 2 based on genome sequence analysis. Current microbiology 2009 Jan;58(1):11-7.
[15]陈国强,陆承平,等.猪链球菌2型溶血素的提纯及其生物学特性.中国人兽共患病杂志2001；17(5)：75-7.
[16]King SJ, Heath PJ, Luque I, et al. Distribution and genetic diversity of suilysin in Streptococcus suis isolated from different diseases of pigs and characterization of the genetic basis of suilysin absence. Infection and immunity 2001 Dec;69(12):7572-82.
[17]De Boer GF. Swinepox. Virus isolation, experimental infections and the differentiation from vaccinia virus infections. Archives of virology 1975;49(2-3):141-50.
[18]Massung RF, Mover RW. The molecular biology of swinepox virus. II. The infectious cycle. Virology 1991 Jan;180(1):355-64.
[19]Datt NS. Comparative Studies of Pigpox and Vaccinia Viruses. I. Host Range Pathogenicity. Journal of comparative pathology 1964 Jan;74:62-9.
[20]Datt NS. Comparative Studies of Pigpox and Vaccinia Viruses. Ii. Serological Relationship. Journal of comparative pathology 1964 Jan;74:70-80.
[21]Shope RE. Swine pox. Archives of virology 1940;1(4):457-67.
[22]Cheville NF. Immunofluorescent and morphologic studies on swinepox. Pathologia veterinaria 1966;3(5):556-64.
[23]Bertholet C, Drillien R, Wittek R. One hundred base pairs of 5' flanking sequence of a vaccinia virus late gene are sufficient to temporally regulate late transcription. Proceedings of the National Academy of Sciences of the United States of America 1985 Apr;82(7):2096-100.
[24]Davison AJ, Moss B. Structure of vaccinia virus late promoters. Journal of molecular biology 1989 Dec 20;210(4):771-84.
[25]Gu H, Zhu H, Lu C. Use of in vivo-induced antigen technology (IVIAT) for the identification of Streptococcus suis serotype 2 in vivo-induced bacterial protein antigens. BMC microbiology 2009;9:201.
[26]Garibaldi M, Rodriguez-Ortega MJ, Mandanici F, et al. Immunoprotective activities of a Streptococcus suis pilus subunit in murine models of infection. Vaccine 2010 Apr 30;28(20):3609-16.
[27]Moss B. Genetically engineered poxviruses for recombinant gene expression, vaccination, and safety. Proceedings of the National Academy of Sciences of the United States of America 1996 Oct 15;93(21):11341-8.
[28]Paoletti E. Applications of pox virus vectors to vaccination:an update. Proceedings of the National Academy of Sciences of the United States of America 1996 Oct 15;93(21):11349-53.
[29]Yamanouchi K, Barrett T, Kai C. New approaches to the development of virus vaccines for veterinary use. Revue scientifique et technique (International Office of Epizootics) 1998 Dec; 17(3):641-53.
[30]Barcena J, Blasco R. Recombinant swinepox virus expressing beta-galactosidase:investigation of viral host range and gene expression levels in cell culture. Virology 1998 Apr 10;243(2):396-405.
[31]Xu L, Huang B, Du H, et al. Crystal structure of cytotoxin protein suilysin from Streptococcus suis. Protein & cell Jan; 1 (1):96-105.
[32]Staats JJ, Plattner BL, Stewart GC, et al. Presence of the Streptococcus suis suilysin gene and expression of MRP and EF correlates with high virulence in Streptococcus suis type 2 isolates. Veterinary microbiology 1999 Dec;70(3-4):201-11.
[33]Charland N, Nizet V, Rubens CE, et al. Streptococcus suis serotype 2 interactions with human brain microvascular endothelial cells. Infection and immunity 2000 Feb;68(2):637-43.
[34]Lalonde M, Segura M, Lacouture S, et al. Interactions between Streptococcus suis serotype 2 and different epithelial cell lines. Microbiology (Reading, England) 2000 Aug;146 (Pt 8):1913-21.
[35]Segura M, Gottschalk M. Streptococcus suis interactions with the murine macrophage cell line J774:adhesion and cytotoxicity. Infection and immunity 2002 Aug;70(8):4312-22.
[36]孙学强.马疱疹病毒1型感染性克隆及表达猪链球菌2型亚单位重组病毒的构建.2010.
[37]范红结,陆承平,唐家琪.猪链球菌2型mrp基因免疫功能片段的克隆、表达及动物试验.微生物学报2004；44(1)：54-7.
[38]Smith HE, Vecht U, Gielkens AL, et al. Cloning and nucleotide sequence of the gene encoding the 136-kilodalton surface protein (muramidase-released protein) of Streptococcus suis type 2. Infection and immunity 1992 Jun;60(6):2361-7.
[39]欧瑜,陆承平.猪链球菌2型溶菌酶释放蛋白基因片段的克隆与表达.农业生物技术学报2002；10(1)：72-5.
[1]Holden MT, Hauser H, Sanders M, et al. Rapid evolution of virulence and drug resistance in the emerging zoonotic pathogen Streptococcus suis. PloS one 2009;4(7):e6072.
[2]Jacobs AA, van den Berg AJ, Loeffen PL. Protection of experimentally infected pigs by suilysin, the thiol-activated haemolysin of Streptococcus suis. The Veterinary record 1996 Sep 7;139(10):225-8.
[3]Wisselink HJ, Vecht U, Stockhofe-Zurwieden N, et al. Protection of pigs against challenge with virulent Streptococcus suis serotype 2 strains by a muramidase-released protein and extracellular factor vaccine. The Veterinary record 2001 Apr 14;148(15):473-7.
[4]Okwumabua O, Chinnapapakkagari S. Identification of the gene encoding a 38-kilodalton immunogenic and protective antigen of Streptococcus suis. Clinical and diagnostic laboratory immunology 2005 Apr;12(4):484-90.
[5]Li Y, Gottschalk M, Esgleas M, et al. Immunization with recombinant Sao protein confers protection against Streptococcus suis infection. Clin Vaccine Immunol 2007 Aug;14(8):937-43.
[6]Feng Y, Pan X, Sun W, et al. Streptococcus suis enolase functions as a protective antigen displayed on the bacterial cell surface. The Journal of infectious diseases 2009 Nov 15;200(10):1583-92.
[7]Tan C, Liu M, Liu J, et al. Vaccination with Streptococcus suis serotype 2 recombinant 6PGD protein provides protection against S. suis infection in swine. FEMS microbiology letters 2009 Jul;296(1):78-83.
[8]Zhang A, Chen B, Li R, et al. Identification of a surface protective antigen, HP0197 of Streptococcus suis serotype 2. Vaccine 2009 Aug 20;27(38):5209-13.
[9]Garibaldi M, Rodriguez-Ortega MJ, Mandanici F, et al. Immunoprotective activities of a Streptococcus suis pilus subunit in murine models of infection. Vaccine 2010 Apr 30;28(20):3609-16.
[10]Vatter H, Mursch K, Zimmermann M, et al. Endothelin-converting enzyme activity in human cerebral circulation. Neurosurgery 2002 Aug;51(2):445-51; discussion 51-2.
[11]Awano S, Ansai T, Mochizuki H, et al. Sequencing, expression and biochemical characterization of the Porphyromonas gingivalis pepO gene encoding a protein homologous to human endothelin-converting enzyme. FEBS letters 1999 Oct 22;460(1):139-44.
[12]Froeliger EH, Oetjen J, Bond JP, et al. Streptococcus parasanguis pepO encodes an endopeptidase with structure and activity similar to those of enzymes that modulate peptide receptor signaling in eukaryotic cells. Infection and immunity 1999 Oct;67(10):5206-14.
[13]Mierau I, Tan PS, Haandrikman AJ, et al. Cloning and sequencing of the gene for a lactococcal endopeptidase, an enzyme with sequence similarity to mammalian enkephalinase. Journal of bacteriology 1993 Apr; 175(7):2087-96.
[14]Oetjen J, Fives-Taylor P, Froeliger E. Characterization of a streptococcal endopeptidase with homology to human endothelin-converting enzyme. Infection and immunity 2001 Jan;69(1):58-64.
[15]Rawlings ND, Barrett AJ. Evolutionary families of metallopeptidases. Methods in enzymology 1995;248:183-228.
[16]Zhang W, Lu CP. Immunoproteomics of extracellular proteins of Chinese virulent strains of Streptococcus suis type 2. Proteomics 2007 Dec;7(24):4468-76.
[17]Zhang W, Lu CP. Immunoproteomic assay of membrane-associated proteins of Streptococcus suis type 2 China vaccine strain HA9801. Zoonoses and public health 2007;54(6-7):253-9.
[18]谭臣.猪链球菌2型ECE1的致病性及6PGD蛋白的免疫原性研究.华中农业大学博士学位论文2010.
[19]De Boer GF. Swinepox. Virus isolation, experimental infections and the differentiation from vaccinia virus infections. Archives of virology 1975;49(2-3):141-50.
[20]Massung RF, Moyer RW. The molecular biology of swinepox virus. II. The infectious cycle. Virology 1991 Jan;180(1):355-64.
[21]Datt NS. Comparative Studies of Pigpox and Vaccinia Viruses. I. Host Range Pathogenicity. Journal of comparative pathology 1964 Jan;74:62-9.
[22]Datt NS. Comparative Studies of Pigpox and Vaccinia Viruses. Ii. Serological Relationship. Journal of comparative pathology 1964 Jan;74:70-80.
[23]Shope RE. Swine pox. Archives of virology 1940;1(4):457-67.
[24]Bertholet C, Drillien R, Wittek R. One hundred base pairs of 5' flanking sequence of a vaccinia virus late gene are sufficient to temporally regulate late transcription. Proceedings of the National Academy of Sciences of the United States of America 1985 Apr;82(7):2096-100.
[25]Davison AJ, Moss B. Structure of vaccinia virus late promoters. Journal of molecular biology 1989 Dec 20;210(4):771-84.
[26]Gu H, Zhu H, Lu C. Use of in vivo-induced antigen technology (IVIAT) for the identification of Streptococcus suis serotype 2 in vivo-induced bacterial protein antigens. BMC microbiology 2009;9:201.
[27]Chanter N, Jones PW, Alexander TJ. Meningitis in pigs caused by Streptococcus suis--a speculative review. Veterinary microbiology 1993 Jul;36(1-2):39-55.
[28]Staats JJ, Feder I, Okwumabua O, et al. Streptococcus suis:past and present. Veterinary research communications 1997 Aug;21(6):381-407.
[29]Gottschalk M, Segura M. The pathogenesis of the meningitis caused by Streptococcus suis:the unresolved questions. Veterinary microbiology 2000 Oct 1;76(3):259-72.
[30]陆承平,姚火春,范红结,et al.猪链球菌致病性研究及其公共卫生意义.中国预防医学杂志2006；7(4)：361-2.
[31]Gottschalk M. Streptococcus suis Infections in Humans:What is the prognosis for Western countries? (Part I). Clinical Microbiology Newsletter 2010 Jun;32(12):89-96.
[32]Fittipaldi N, Fuller TE, Teel JF, et al. Serotype distribution and production of muramidase-released protein, extracellular factor and suilysin by field strains of Streptococcus suis isolated in the United States. Veterinary microbiology 2009 Nov 18;139(3-4):310-7.
[33]Gottschalk M. Streptococcus suis Infections in Humans:What is the prognosis for Western countries? (Part II). Clinical Microbiology Newsletter 2010.
[34]Sriskandan S, Slater JD. Invasive disease and toxic shock due to zoonotic Streptococcus suis:an emerging infection in the East? PLoS medicine 2006 May;3(5):e187.