H5亚型血凝素单抗库的构建、广谱中和单抗的发现及其对H5N1禽流感的治疗研究
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摘要
2003年以来，高致病性H5N1禽流感病毒(H5N1病毒)在禽类中的持续流行和不断发生的人类感染事件使人们担心H5N1病毒可能持续进化成引发人类流感大流行的大流感病毒株。为此，研制H5N1病毒的疫苗和抗体治疗药物成为当前应对H5N1病毒引发潜在流感大流行的研究热点，而H5N1病毒最主要的中和抗体来自于表面糖蛋白血凝素(HA)，因此HA成为主要研究靶标。
H5N1病毒具有高度变异性，故疫苗研制的关键是疫苗株的选择。根据分子进化树分析预测结果显示H5N1病毒HA基因已演变成至少10种不同抗原性特征的变异分支(Clade 0-9)。虽然病毒抗血清可真实地反映出病毒的抗原性表现型，但是H5N1病毒新变异株的不断出现和低免疫原性特点使及时制备各种雪貂抗血清变得困难。建立一个H5亚型血凝素单抗库(H5 MAb Panel)，将有助于H5N1病毒新流行株的抗原性变异监测，并指导疫苗株的选择。为此开展了如下工作：(1)利用分子进化树分析1997～2007年分离的114株H5N1病毒的HA基因，并选择位于进化树不同分支的40株H5N1病毒代表株(H5N1 Virus Panel)用于单抗的制备和鉴定；(2)利用Clade 1、2-1、2．2、2．3、8等五种变异分支的H5N1病毒免疫和筛选，建立一个包含476株单抗的H5亚型血凝素单抗库；(3)利用血凝抑制试验(HI)分析476株H5单抗对40株H5N1病毒的反应性，把单抗分成九种反应类型(M1-M9)，并发现60株属于M1、M2类的“广谱单抗”能与40株病毒全部或基本全部反应；(4)从中选出15株代表性单抗组成H5 MAbPanel对40株H5N1病毒进行细胞中和试验分析，进一步把15株单抗分成三类，代表H5 MAb三种不同的表位识别特征(Ⅰ、Ⅱ、Ⅲ)，其中“广谱单抗”属于第Ⅰ类；(5)细胞中和试验结果反映了H5N1病毒的抗原性特征，并把40株H5N1病毒分成四类，代表H5亚型血凝素的四种不同抗原性(A、B、C、D)。A类病毒大部分为Clade 2．1(印尼流行株)；B类病毒最具多样性，除了Clade 1(越南流行株)，还包括Clade 0、4、5、7、8、9等；C类病毒主要为Clade 2．2(青海类似株，QH-like)；D类主要是Clade 2．3．4(福建类似株，FJ-like)。总之，本研究成功建立了一个H5 MAb Panel，可为H5N1病毒的变异监控、抗原性分析和疫苗株选择更新提供有用的研究工具。
人类感染H5N1病毒具有高致死率，可能原因是病毒感染人体后会迅速扩散到体内多个组织器官，导致严重的并发症。流感病毒传统的抗病毒治疗药物(离子通道抑制剂和神经氨酸酶抑制剂)对H5N1病毒疗效一般，且疗效依赖于病毒感染早期或感染之前开始用药，而实际临床病人一般都在出现症状的发病中后期才被发现。因此寻找H5N1病毒的治疗新途径势在必行。近年来，被动免疫日益被用于治疗急性传染病，利用中和抗体快速清除体内病毒，因此H5血凝素中和单抗成为治疗H5N1病毒的一种选择。鉴于H5N1病毒HA抗原性存在多种变异分支，理想的治疗单抗应对不同变异分支有广谱疗效。为此在H5N1病毒动物感染模型中对上述获得的H5广谱单抗进行治疗研究：(1)建立了H5N1病毒动物感染模型(BALB／c小鼠和家猫)，确定了病毒对动物的一周致死剂量，鉴定了广谱单抗及其片段在不同动物体内半衰期等生物学性质，选择13D4、13D4F(ab’)_2开展治疗研究；(2)在小鼠体内证明广谱单抗13D4对Clade 1、2．1、2．2、2．3等已引发人类感染的四种变异分支的H5N1病毒感染均有良好疗效，显示了广谱疗效，而且疗效与单抗给药时间和剂量有关，越早给药，用药剂量越小；(3)组织病毒滴度分离研究显示，广谱单抗在体内能高效清除病毒，使得单抗在病毒引发肺外多器官感染时仍有效，单抗能在病毒感染24小时内将肺组织中的病毒完全清除；(4)利用片段单抗13D4 F(ab’)_2治疗H5N1病毒感染鼠，显示疗效不如13D4全抗体，但明显优于抗流感病毒药物奥赛米韦(达菲)；(5)进一步比较不同抗体亚类广谱单抗对H5N1病毒感染鼠的治疗效果，发现IgG2a和IgG2b亚类的疗效明显好于IgG1，而IgM和IgG3亚类无疗效，提示广谱单抗的治疗机制可能与抗体Fc段介导的ADCC、补体激活或免疫调理有关；(6)单抗13D4还对H5N1病毒感染家猫有良好的异源抗体治疗效果；(7)为认识广谱单抗识别的保守表位，利用逃逸突变分析方法鉴定出单抗13D4至少结合两个位点氨基酸(第152位和第182位)，相应突变株对小鼠的毒力均下降，提示这两个位点与病毒受体结合区有关；(8)HI试验显示任意一个点的突变病毒株均不能完全逃避单抗13D4的结合，动物实验显示单抗13D4对逃逸病毒感染鼠虽疗效下降但仍可有效保护。总之，本研究获得的13D4等H5亚型血凝素广谱中和单抗对同源和异源动物感染H5N1病毒均有良好疗效，而且广谱单抗通过结合H5N1病毒血凝素上至少2个保守的关键位点，增强了单抗应对病毒单一突变的治疗能力。
Long-term endemicity of highly pathogenic avian influenza H5N1 viruses inbirds and sporadic human transmissions by H5N 1 viruses since 2003 have raised theconcern of a potential pandemic. It has been explored actively in the development ofthe H5N1 pre-pandemic vaccine and treatment. Hemagglutinin (HA) of H5N1 virus isthe key protein producing neutralizing antibody and becomes a hot target.
Given the high variation, the key work is to select an ideal virus candidate forvaccine development. Based on phylogeneitc analysis of HA sequence, H5N 1 viruseshave been divided into at least 10 genetical clades. The antibody was traditionallyused to analysis the real antigenecity of virus, however, co-circulation of multipleantigenic variants of H5N1 virus and low immunogenecity of H5N1 viurs hamper thetimely production of standard H5N 1-specific ferret antisera. Thus, it is useful toestablish a panel of H5 HA specific MAb for antigenic analysis and vaccine selectionof H5N1 virus. The result as bellows: A panel of 476 H5 HA specific MAb has beenestablished and characterized by HI assay to 40 H5N1 viruses representing differentgenetic lineages from 1997 to 2007. A panel of 60 broadly cross-reactive MAbs havebeen found due to their almost cross-reactive with all the 40 H5N1 virus. Accordingto their HI reactive spectrums, 15 representive MAbs were further selected as a panelto characterize the antigenecity of H5N1 virus. Four antigenic groups, A, B C and D,were identified among 40 H5N1 viruses based on their cross-reactive spectra with thispanel of MAbs in neutralisation assay. Group A consists mostly of clade 2.1 viruses,which are circulating mainly in Indonesia; Group B consists of the most geneticallydiversified variants, including viruses from clade 0, 1,4, 5, 7 and 9; Group C containsprimarily clade 2.2 Qinghai-like viruses; and Group D is composed almostexclusively of clade 2.3.4 Fujian-like viruses. In summary, this study established auseful panel of H5 HA MAbs and will facilitate for the recognition of emergingantigenic variants of the H5N 1 virus and help in the selection or evaluation of vaccinestrains.
Human H5N 1 infections cause rapid dissemination of virus to multiple organsand are associated with severe disease and high mortality. Difficulties of currentanti-viral drugs, such as ion channel blockers and neuraminidase inhibitors, intreatment and high mortality rates may be attributable to failures in rapidneutralization and control dissemination of H5N1 virus in humans after symptoms emerge. Passive immunotherapy has been used increasingly in treatment of infectiousdiseases. However, to achieve neutralization, therapeutic antibodies rely on theirspecific binding to epitopes in the HA protein of influenza viruses. Continuousevolution and co-circulation of multiple genetic H5N1 lineages in broad regions have,however, generated antigenically diverse variants that pose significant challenges fordeveloping broadly cross protective therapeutic MAbs. Thus, the ideal therapeuticalantibody is the broadly cross-reactive H5 specific MAbs. One of these MAbs, 13D4,has been demonstrated to protect mice against lethal challenge by 4 H5N 1 strainsrepresenting the current major genetic populations, clades 1,2.1,2.2, and 2.3, even ata stage of infection when H5N1 virus has disseminated beyond the pulmonary system.Complete neutralization of virus in lung tissue of infected animals was observed 24 hafter treatment with 13D4. Compared the protection efficacy between differentisotypes of cross-reactive MAb, it was found that both IgG2a and IgG2b are betterthan IgG 1,IgM, IgG3. This suggested that Fc fragment of MAb may be related toprotection. Further study also showed that efficacy of F(ab')_2 is less than wholeantibody but better than oseltamivir (Tamiflu) in protect H5N1 infected mice. It wasalso observed that MAb 13D4 provide a good heterologous protection efficacy forH5N 1 infected cat. Mapping of this MAb with escape mutants showed it to bind to 2conserved, possibly critical, sites of H5N1 hemagglutinin, 152 and 182. It was alsofound that their escape mutants were partially attenuated in mice. Such evidencesupports the idea that these sites may be critical to virus function. HI assay showedthese escape mutants still retain hemagglutination inhibition, albeit at a lower levelthan their parental viruses. 13D4 MAb was still able to protect mice against a lethalchallenge of N182K virus, although with lower efficiency. In summary, H5broad-reactive MAbs such as 13D4 may lie in the fact that they target conserved,critical, and, therefore, preserved HA antigenic sites in H5N1 viruses and may havetherapeutic value in controlling infection due to current and future H5N1 variants.
H5N1病毒具有高度变异性，故疫苗研制的关键是疫苗株的选择。根据分子进化树分析预测结果显示H5N1病毒HA基因已演变成至少10种不同抗原性特征的变异分支(Clade 0-9)。虽然病毒抗血清可真实地反映出病毒的抗原性表现型，但是H5N1病毒新变异株的不断出现和低免疫原性特点使及时制备各种雪貂抗血清变得困难。建立一个H5亚型血凝素单抗库(H5 MAb Panel)，将有助于H5N1病毒新流行株的抗原性变异监测，并指导疫苗株的选择。为此开展了如下工作：(1)利用分子进化树分析1997～2007年分离的114株H5N1病毒的HA基因，并选择位于进化树不同分支的40株H5N1病毒代表株(H5N1 Virus Panel)用于单抗的制备和鉴定；(2)利用Clade 1、2-1、2．2、2．3、8等五种变异分支的H5N1病毒免疫和筛选，建立一个包含476株单抗的H5亚型血凝素单抗库；(3)利用血凝抑制试验(HI)分析476株H5单抗对40株H5N1病毒的反应性，把单抗分成九种反应类型(M1-M9)，并发现60株属于M1、M2类的“广谱单抗”能与40株病毒全部或基本全部反应；(4)从中选出15株代表性单抗组成H5 MAbPanel对40株H5N1病毒进行细胞中和试验分析，进一步把15株单抗分成三类，代表H5 MAb三种不同的表位识别特征(Ⅰ、Ⅱ、Ⅲ)，其中“广谱单抗”属于第Ⅰ类；(5)细胞中和试验结果反映了H5N1病毒的抗原性特征，并把40株H5N1病毒分成四类，代表H5亚型血凝素的四种不同抗原性(A、B、C、D)。A类病毒大部分为Clade 2．1(印尼流行株)；B类病毒最具多样性，除了Clade 1(越南流行株)，还包括Clade 0、4、5、7、8、9等；C类病毒主要为Clade 2．2(青海类似株，QH-like)；D类主要是Clade 2．3．4(福建类似株，FJ-like)。总之，本研究成功建立了一个H5 MAb Panel，可为H5N1病毒的变异监控、抗原性分析和疫苗株选择更新提供有用的研究工具。
人类感染H5N1病毒具有高致死率，可能原因是病毒感染人体后会迅速扩散到体内多个组织器官，导致严重的并发症。流感病毒传统的抗病毒治疗药物(离子通道抑制剂和神经氨酸酶抑制剂)对H5N1病毒疗效一般，且疗效依赖于病毒感染早期或感染之前开始用药，而实际临床病人一般都在出现症状的发病中后期才被发现。因此寻找H5N1病毒的治疗新途径势在必行。近年来，被动免疫日益被用于治疗急性传染病，利用中和抗体快速清除体内病毒，因此H5血凝素中和单抗成为治疗H5N1病毒的一种选择。鉴于H5N1病毒HA抗原性存在多种变异分支，理想的治疗单抗应对不同变异分支有广谱疗效。为此在H5N1病毒动物感染模型中对上述获得的H5广谱单抗进行治疗研究：(1)建立了H5N1病毒动物感染模型(BALB／c小鼠和家猫)，确定了病毒对动物的一周致死剂量，鉴定了广谱单抗及其片段在不同动物体内半衰期等生物学性质，选择13D4、13D4F(ab’)_2开展治疗研究；(2)在小鼠体内证明广谱单抗13D4对Clade 1、2．1、2．2、2．3等已引发人类感染的四种变异分支的H5N1病毒感染均有良好疗效，显示了广谱疗效，而且疗效与单抗给药时间和剂量有关，越早给药，用药剂量越小；(3)组织病毒滴度分离研究显示，广谱单抗在体内能高效清除病毒，使得单抗在病毒引发肺外多器官感染时仍有效，单抗能在病毒感染24小时内将肺组织中的病毒完全清除；(4)利用片段单抗13D4 F(ab’)_2治疗H5N1病毒感染鼠，显示疗效不如13D4全抗体，但明显优于抗流感病毒药物奥赛米韦(达菲)；(5)进一步比较不同抗体亚类广谱单抗对H5N1病毒感染鼠的治疗效果，发现IgG2a和IgG2b亚类的疗效明显好于IgG1，而IgM和IgG3亚类无疗效，提示广谱单抗的治疗机制可能与抗体Fc段介导的ADCC、补体激活或免疫调理有关；(6)单抗13D4还对H5N1病毒感染家猫有良好的异源抗体治疗效果；(7)为认识广谱单抗识别的保守表位，利用逃逸突变分析方法鉴定出单抗13D4至少结合两个位点氨基酸(第152位和第182位)，相应突变株对小鼠的毒力均下降，提示这两个位点与病毒受体结合区有关；(8)HI试验显示任意一个点的突变病毒株均不能完全逃避单抗13D4的结合，动物实验显示单抗13D4对逃逸病毒感染鼠虽疗效下降但仍可有效保护。总之，本研究获得的13D4等H5亚型血凝素广谱中和单抗对同源和异源动物感染H5N1病毒均有良好疗效，而且广谱单抗通过结合H5N1病毒血凝素上至少2个保守的关键位点，增强了单抗应对病毒单一突变的治疗能力。
Long-term endemicity of highly pathogenic avian influenza H5N1 viruses inbirds and sporadic human transmissions by H5N 1 viruses since 2003 have raised theconcern of a potential pandemic. It has been explored actively in the development ofthe H5N1 pre-pandemic vaccine and treatment. Hemagglutinin (HA) of H5N1 virus isthe key protein producing neutralizing antibody and becomes a hot target.
Given the high variation, the key work is to select an ideal virus candidate forvaccine development. Based on phylogeneitc analysis of HA sequence, H5N 1 viruseshave been divided into at least 10 genetical clades. The antibody was traditionallyused to analysis the real antigenecity of virus, however, co-circulation of multipleantigenic variants of H5N1 virus and low immunogenecity of H5N1 viurs hamper thetimely production of standard H5N 1-specific ferret antisera. Thus, it is useful toestablish a panel of H5 HA specific MAb for antigenic analysis and vaccine selectionof H5N1 virus. The result as bellows: A panel of 476 H5 HA specific MAb has beenestablished and characterized by HI assay to 40 H5N1 viruses representing differentgenetic lineages from 1997 to 2007. A panel of 60 broadly cross-reactive MAbs havebeen found due to their almost cross-reactive with all the 40 H5N1 virus. Accordingto their HI reactive spectrums, 15 representive MAbs were further selected as a panelto characterize the antigenecity of H5N1 virus. Four antigenic groups, A, B C and D,were identified among 40 H5N1 viruses based on their cross-reactive spectra with thispanel of MAbs in neutralisation assay. Group A consists mostly of clade 2.1 viruses,which are circulating mainly in Indonesia; Group B consists of the most geneticallydiversified variants, including viruses from clade 0, 1,4, 5, 7 and 9; Group C containsprimarily clade 2.2 Qinghai-like viruses; and Group D is composed almostexclusively of clade 2.3.4 Fujian-like viruses. In summary, this study established auseful panel of H5 HA MAbs and will facilitate for the recognition of emergingantigenic variants of the H5N 1 virus and help in the selection or evaluation of vaccinestrains.
Human H5N 1 infections cause rapid dissemination of virus to multiple organsand are associated with severe disease and high mortality. Difficulties of currentanti-viral drugs, such as ion channel blockers and neuraminidase inhibitors, intreatment and high mortality rates may be attributable to failures in rapidneutralization and control dissemination of H5N1 virus in humans after symptoms emerge. Passive immunotherapy has been used increasingly in treatment of infectiousdiseases. However, to achieve neutralization, therapeutic antibodies rely on theirspecific binding to epitopes in the HA protein of influenza viruses. Continuousevolution and co-circulation of multiple genetic H5N1 lineages in broad regions have,however, generated antigenically diverse variants that pose significant challenges fordeveloping broadly cross protective therapeutic MAbs. Thus, the ideal therapeuticalantibody is the broadly cross-reactive H5 specific MAbs. One of these MAbs, 13D4,has been demonstrated to protect mice against lethal challenge by 4 H5N 1 strainsrepresenting the current major genetic populations, clades 1,2.1,2.2, and 2.3, even ata stage of infection when H5N1 virus has disseminated beyond the pulmonary system.Complete neutralization of virus in lung tissue of infected animals was observed 24 hafter treatment with 13D4. Compared the protection efficacy between differentisotypes of cross-reactive MAb, it was found that both IgG2a and IgG2b are betterthan IgG 1,IgM, IgG3. This suggested that Fc fragment of MAb may be related toprotection. Further study also showed that efficacy of F(ab')_2 is less than wholeantibody but better than oseltamivir (Tamiflu) in protect H5N1 infected mice. It wasalso observed that MAb 13D4 provide a good heterologous protection efficacy forH5N 1 infected cat. Mapping of this MAb with escape mutants showed it to bind to 2conserved, possibly critical, sites of H5N1 hemagglutinin, 152 and 182. It was alsofound that their escape mutants were partially attenuated in mice. Such evidencesupports the idea that these sites may be critical to virus function. HI assay showedthese escape mutants still retain hemagglutination inhibition, albeit at a lower levelthan their parental viruses. 13D4 MAb was still able to protect mice against a lethalchallenge of N182K virus, although with lower efficiency. In summary, H5broad-reactive MAbs such as 13D4 may lie in the fact that they target conserved,critical, and, therefore, preserved HA antigenic sites in H5N1 viruses and may havetherapeutic value in controlling infection due to current and future H5N1 variants.
引文
[1] Li KS, Guan Y, Wang J, Smith GJ, Xu KM, Duan L, et al. Genesis of a highly pathogenic and potentially pandemic H5N1 influenza virus in eastern Asia. Nature 2004;430(6996):209-13.
[2] Ligon BL. Avian influenza virus H5N1: a review of its history and information regarding its potential to cause the next pandemic. Semin Pediatr Infect Dis 2005;16(4):326-35.
[3] Peiris JS, de Jong MD, Guan Y. Avian influenza virus (H5N1): a threat to human health. Clin Microbiol Rev 2007;20(2):243-67.
[4] WHO-Cumulative-Number-20080910. World Health Organization (WHO). Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) Reported to WHO, (10 September 2008). http://www.who.mt/csr/disease/avianinfluenza/country/en/index.html.
[5] Leneva IA, Roberts N, Govorkova EA, Goloubeva OG, Webster RG. The neuraminidase inhibitor GS4104 (oseltamivir phosphate) is efficacious against A/Hong Kong/156/97 (H5N1) and A/Hong Kong/1074/99 (H9N2) influenza viruses. Antiviral Res 2000;48(2):101-15.
[6] Gubareva LV, Webster RG, Hayden FG. Comparison of the activities of zanamivir, oseltamivir, and RWJ-270201 against clinical isolates of influenza virus and neuraminidase inhibitor-resistant variants. Antimicrob Agents Chemother 2001 ;45(12):3403-8.
[7] Sugaya N, Mitamura K, Yamazaki M, Tamura D, Ichikawa M, Kimura K, et al. Lower clinical effectiveness of oseltamivir against influenza B contrasted with influenza A infection in children. Clin Infect Dis 2007;44(2):197-202.
[8] Abdel-Ghafar AN, Chotpitayasunondh T, Gao Z, Hayden FG, Nguyen DH, de Jong MD, et al. Update on avian influenza A (H5N1) virus infection in humans. N Engl J Med 2008;358(3):261-73.
[9] Schun(?)mann HJ, Hill SR, Kakad M, Bellamy R, Uyeki TM, Hayden FG, et al. WHO Rapid Advice Guidelines for pharmacological management of sporadic human infection with avian influenza A (H5N1) virus. Lancet Infect Dis 2007;7(l):21-31.
[10] de Jong MD, Tran TT, Truong HK, Vo MH, Smith GJ, Nguyen VC, et al. Oseltamivir resistance during treatment of influenza A (H5N1) infection. N Engl J Med 2005;353(25):2667-72.
[11] Marasco WA, Sui J. The growth and potential of human antiviral monoclonal antibody therapeutics. Nat Biotechnol 2007;25(12):1421-34.
[12] Luke TC, Kilbane EM, Jackson JL, Hoffman SL. Meta-analysis: convalescent blood products for Spanish influenza pneumonia: a future H5N1 treatment? Ann Intern Med 2006;145(8):599-609.
[13] Zhou B, Zhong N, Guan Y. Treatment with convalescent plasma for influenza A (H5N1) infection. N Engl J Med 2007;357(14):1450-1.
[14] Lamb-Krug-FieldsVirology. Lamb RA, Krug RM. Orthomyxoviridae: The viruses and their replication. In: Fields Virology, fourth edition. Knipe DM, Howley PM eds, Lippincott, Philadelphia 2001,pp 1487-1531..
[15] Chen H, Smith GJ, Li KS, Wang J, Fan XH, Rayner JM, et al. Establishment of multiple sublineages of H5N1 influenza virus in Asia: implications for pandemic control. Proc Natl Acad Sci U S A2006;103(8):2845-50.
[16] Smith GJ, Fan XH, Wang J, Li KS, Qin K, Zhang JX, et al. Emergence and predominance of an H5N1 influenza variant in China. Proc Natl Acad Sci U S A 2006; 103(45): 16936-41.
[17] WHO-EID-nomenclature-system. World Health Organization (WHO). Toward a unified nomenclature system for highly pathogenic avian influenza virus (H5N1). Emerg Infect Dis 2008;14(7):el.
[18] Wright-Webster-Fields Virology. Wright PF, Webster RG. Orthomyxoviruses. In: Fields Virology, fourth edition. Knipe DM, Howley PM eds, Lippincott, Philadelphia 2001, pp 1533-1579.
[19] A revision of the system of nomenclature for influenza viruses: a WHO memorandum. Bull World Health Organ 1980;58(4):585-91.
[20] Chen W, Calvo PA, Malide D, Gibbs J, Schubert U, Bacik I, et al. A novel influenza A virus mitochondrial protein that induces cell death. Nat Med 2001;7(12):1306-12.
[21] InfluenzaReport2006. Ortrud Werner and Timm C. Harder. Avian Influenza: Influenza Report 2006. edited by Bernd Sebastian Kamps, Christian Hoffmann, Wolfgang Preiser. Flying Publisher..
[22] Nicholson KG, Wood JM, Zambon M. Influenza. Lancet 2003;362(9397):1733-45.
[23] Stevens J, Corper AL, Basler CF, Taubenberger JK, Palese P, Wilson IA. Structure of the uncleaved human H1 hemagglutinin from the extinct 1918 influenza virus. Science 2004;303(5665):1866-70.
[24] Gamblin SJ, Haire LF, Russell RJ, Stevens DJ, Xiao B, Ha Y, et al. The structure and receptor binding properties of the 1918 influenza hemagglutinin. Science 2004;303(5665):1838-42.
[25] Webster RG, Bean WJ, Gorman OT, Chambers TM, Kawaoka Y. Evolution and ecology of influenza A viruses. Microbiol Rev 1992;56(1):152-79.
[26] Taubenberger JK, Reid AH, Krafft AE, Bijwaard KE, Fanning TG. Initial genetic characterization of the 1918 "Spanish" influenza virus. Science 1997;275(5307):1793-6.
[27] Johnson NP, Mueller J. Updating the accounts: global mortality of the 1918-1920 "Spanish" influenza pandemic. Bull Hist Med 2002;76(l):105-15.
[28] Connor RJ, Kawaoka Y, Webster RG, Paulson JC. Receptor specificity in human, avian, and equine H2 and H3 influenza virus isolates. Virology 1994;205(l):17-23.
[29] Matrosovich MN, Gambaryan AS, Teneberg S, Piskarev VE, Yamnikova SS, Lvov DK, et al. Avian influenza A viruses differ from human viruses by recognition of sialyloligosaccharides and gangliosides and by a higher conservation of the HA receptor-binding site. Virology 1997;233(l):224-34.
[30] Hatta M, Gao P, Halfmann P, Kawaoka Y. Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses. Science 2001;293(5536):1840-2.
[31] Ennis FA, Cruz J, Jameson J, Klein M, Burt D, Thipphawong J. Augmentation of human influenza A virus-specific cytotoxic T lymphocyte memory by influenza vaccine and adjuvanted carriers (ISCOMS). Virology 1999;259(2):256-61.
[32] Brown EG. Influenza virus genetics. Biomed Pharmacother 2000;54(4):196-209.
[33] Seo SH, Hoffmann E, Webster RG Lethal H5N1 influenza viruses escape host anti-viral cytokine responses. Nat Med 2002;8(9):950-4.
[34] Garcia-Sastre A, Egorov A, Matassov D, Brandt S, Levy DE, Durbin JE, et al. Influenza A virus lacking the NS1 gene replicates in interferon-deficient systems. Virology 1998;252(2):324-30.
[35] Nicholson-Textbook-of-Influenza. Nicholson, KG, R. G. Webster, et al. (1998). "Textbook of Influenza." 1st. published by Blackwell Science Ltd.
[36] Frost WH. Statistics of Influenza Morbidity. Public Health Reports 1920;35(l l):584-97.
[37] Simonsen L, Clarke MJ, Schonberger LB, Arden NH, Cox NJ, Fukuda K. Pandemic versus epidemic influenza mortality: a pattern of changing age distribution. J Infect Dis 1998;178(l):53-60.
[38] Horimoto T, Kawaoka Y. Pandemic threat posed by avian influenza A viruses. Clin Microbiol Rev 2001;14(l):129-49.
[39] Taubenberger JK, Reid AH, Lourens RM, Wang R, Jin G, Fanning TG Characterization of the 1918 influenza virus polymerase genes. Nature 2005;437(7060):889-93.
[40] Scholtissek C, Rohde W, Von Hoyningen V, Rott R. On the origin of the human influenza virus subtypes H2N2 and H3N2. Virology 1978;87(l):13-20.
[41] Kawaoka Y, Krauss S, Webster RG. Avian-to-human transmission of the PB1 gene of influenza A viruses in the 1957 and 1968 pandemics. J Virol 1989;63(11):4603-8.
[42] Lupiani B, Reddy SM. The history of avian influenza. Comp Immunol Microbiol Infect Dis 2008.
[43] Alexander DJ. A review of avian influenza in different bird species. Vet Microbiol 2000;74(l-2):3-13.
[44] Klempner MS, Shapiro DS. Crossing the species barrier-one small step to man, one giant leap to mankind. N Engl J Med 2004;350(12):1171-2.
[45] Webster RG, Peiris M, Chen H, Guan Y. H5N1 outbreaks and enzootic influenza. Emerg Infect Dis 2006;12(l):3-8.
[46] Suarez DL. Evolution of avian influenza viruses. Vet Microbiol 2000;74(l -2): 15-27.
[47] Gorman OT, Bean WJ, Kawaoka Y, Webster RG. Evolution of the nucleoprotein gene of influenza A virus. J Virol 1990;64(4):1487-97.
[48] Webster RG, Yakhno M, Hinshaw VS, Bean WJ, Murti KG. Intestinal influenza: replication and characterization of influenza viruses in ducks. Virology 1978;84(2):268-78.
[49] Halvorson DA, Kelleher CJ, Senne DA. Epizootiology of avian influenza: effect of season on incidence in sentinel ducks and domestic turkeys in Minnesota, Appl Environ Microbiol 1985;49(4):914-9.
[50] Sturm-Ramirez KM, Ellis T, Bousfield B, Bissett L, Dyrting K, Rehg JE, et al. Reemerging H5N1 influenza viruses in Hong Kong in 2002 are highly pathogenic to ducks. J Virol 2004;78(9):4892-901.
[51] Stohr K. Avian influenza and pandemics-research needs and opportunities. N Engl J Med 2005;352(4):405-7.
[52] Chen H, Smith GJ, Zhang SY, Qin K, Wang J, Li KS, et al. Avian flu: H5N1 virus outbreak in migratory waterfowl. Nature 2005;436(7048):191-2.
[53] Liu J, Xiao H, Lei F, Zhu Q, Qin K, Zhang XW, et al. Highly pathogenic H5N1 influenza virus infection in migratory birds. Science 2005;309(5738):1206.
[54] Li KS, Xu KM, Peiris JS, Poon LL, Yu KZ, Yuen KY, et al. Characterization of H9 subtype influenza viruses from the ducks of southern China: a candidate for the next influenza pandemic in humans? J Virol 2003;77(12):6988-94.
[55] Ito T, Couceiro JN, Kelm S, Baum LG, Krauss S, Castrucci MR, et al. Molecular basis for the generation in pigs of influenza A viruses with pandemic potential. J Virol 1998;72(9):7367-73.
[56] Claas EC, Kawaoka Y, de Jong JC, Masurel N, Webster RG Infection of children with avian-human reassortant influenza virus from pigs in Europe. Virology 1994;204(l):453-7.
[57] Hinshaw VS, Bean WJ, Jr., Webster RG, Easterday BC. The prevalence of influenza viruses in swine and the antigenic and genetic relatedness of influenza viruses from man and swine. Virology 1978;84(1):51-62.
[58] Yasuda J, Shortridge KF, Shimizu Y, Kida H. Molecular evidence for a role of domestic ducks in the introduction of avian H3 influenza viruses to pigs in southern China, where the A/Hong Kong/68 (H3N2) strain emerged. J Gen Virol 1991;72 (Pt 8):2007-10.
[59] Bean WJ, Schell M, Katz J, Kawaoka Y, Naeve C, Gorman O, et al. Evolution of the H3 influenza virus hemagglutinin from human and nonhuman hosts. J Virol 1992;66(2): 1129-38.
[60] Pensaert M, Ottis K, Vandeputte J, Kaplan MM, Bachmann PA. Evidence for the natural transmission of influenza A virus from wild ducts to swine and its potential importance for man. Bull World Health Organ 1981;59(l):75-8.
[61] Scholtissek C, Burger H, Bachmann PA, Hanno(?)n C. Genetic relatedness of hemagglutinins of the H1 subtype of influenza A viruses isolated from swine and birds. Virology 1983;129(2):521-3.
[62] Guan Y, Shortridge KF, Krauss S, Li PH, Kawaoka Y, Webster RG Emergence of avian H1N1 influenza viruses in pigs in China. J Virol 1996;70(l l):8041-6.
[63] Peiris JS, Guan Y, Markwell D, Ghose P, Webster RG Shortridge KF. Cocirculation of avian H9N2 and contemporary "human" H3N2 influenza A viruses in pigs in southeastern China: potential for genetic reassortment? J Virol 2001 ;75(20):9679-86.
[64] Ninomiya A, Takada A, Okazaki K, Shortridge KF, Kida H. Seroepidemiological evidence of avian H4, H5, and H9 influenza A virus transmission to pigs in southeastern China. Vet Microbiol 2002;88(2):107-14.
[65] Tumova B, Schild GC. Antigenic relationships between type a influenza viruses of human, porcine, equine, and avian origin. Bull World Health Organ 1972;47(4):453-60.
[66] Kawaoka Y, Webster RG. Origin of the hemagglutinin on A/Equine/Johannesburg/86 (H3N8): the first known equine influenza outbreak in South Africa. Arch Virol 1989; 106(1-2): 159-64.
[67] Guo Y, Wang M, Kawaoka Y, Gorman O, Ito T, Saito T, et al. Characterization of a new avian-like influenza A virus from horses in China. Virology 1992;188(l):245-55.
[68] Webster RG Guo YJ. New influenza virus in horses. Nature 1991;351(6327):527.
[69] Wright-FieldVirology. Wright, P. F., G Neumann, et al. (2007). Orthomyxoviruses. Fields Virology. D. M. Knipe and P. M. Howley. Philadelphia, Wolters Kluwer Health/Lippincott Williams & Wilkins. 2.
[70] Webster RG, Hinshaw VS, Bean WJ, Van Wyke KL, Geraci JR, St Aubin DJ, et al. Characterization of an influenza A virus from seals. Virology 1981;113(2):712-24.
[71] Geraci JR, St Aubin DJ, Barker IK, Webster RG, Hinshaw VS, Bean WJ, et al. Mass mortality of harbor seals: pneumonia associated with influenza A virus. Science 1982;215(4536): 1129-31.
[72] Hinshaw VS, Bean WJ, Webster RG, Rehg JE, Fiorelli P, Early G, et al. Are seals frequently infected with avian influenza viruses? J Virol 1984;51(3):863-5.
[73] Nicholson KG, Nguyen-Van-Tam JS, Ahmed AH, Wiselka MJ, Leese J, Ayres J, et al. Randomised placebo-controlled crossover trial on effect of inactivated influenza vaccine on pulmonary function in asthma. Lancet 1998;351(9099):326-31.
[74] Callan RJ, Early G, Kida H, Hinshaw VS. The appearance of H3 influenza viruses in seals. J Gen Virol 1995;76(Pt1):199-203.
[75] Chambers TM, Yamnikova S, Kawaoka Y, Lvov DK, Webster RG. Antigenic and molecular characterization of subtype H13 hemagglutinin of influenza virus. Virology 1989;172(1): 180-8.
[76] Hinshaw VS, Bean WJ, Geraci J, Fiorelli P, Early G, Webster RG. Characterization of two influenza A viruses from a pilot whale. J Virol 1986;58(2):655-6.
[77] Klingeborn B, Englund L, Rott R, Juntti N, Rockborn G. An avian influenza A virus killing a mammalian species-the mink. Brief report. Arch Virol 1985;86(3-4):347-51.
[78] Keawcharoen J, Oraveerakul K, Kuiken T, Fouchier RA, Amonsin A, Payungporn S, et al. Avian influenza H5N1 in tigers and leopards. Emerg Infect Dis 2004;10(12):2189-91.
[79] Quirk M. Zoo tigers succumb to avian influenza. Lancet Infect Dis 2004;4(12):716.
[80] Thanawongnuwech R, Amonsin A, Tantilertcharoen R, Damrongwatanapokin S, Theamboonlers A, Payungporn S, et al. Probable tiger-to-tiger transmission of avian influenza H5N1. Emerg Infect Dis 2005;ll(5):699-701.
[81] Kuiken T, Rimmelzwaan G, van Riel D, van Amerongen G, Baars M, Fouchier R, et al. Avian H5N1 influenza in cats. Science 2004;306(5694):241.
[82] Shortridge KF, Stuart-Harris CH. An influenza epicentre? Lancet 1982;2(8302):812-3.
[83] Shortridge KF, Zhou NN, Guan Y, Gao P, Ito T, Kawaoka Y, et al. Characterization of avian H5N1 influenza viruses from poultry in Hong Kong. Virology 1998;252(2):331-42.
[84] Xu X, Subbarao, Cox NJ, Guo Y. Genetic characterization of the pathogenic influenza A/Goose/Guangdong/1/96 (H5N1) virus: similarity of its hemagglutinin gene to those of H5N1 viruses from the 1997 outbreaks in Hong Kong. Virology 1999;261(1):15-9.
[85] Sims LD, Ellis TM, Liu KK, Dyrting K, Wong H, Peiris M, et al. Avian influenza in Hong Kong 1997-2002. Avian Dis 2003;47(3 Suppl):832-8.
[86] Claas EC, de Jong JC, van Beek R, Rimmelzwaan GF, Osterhaus AD. Human influenza virus A/HongKong/156/97 (H5N1) infection. Vaccine 1998;16(9-10):977-8.
[87] Peiris JS, Yu WC, Leung CW, Cheung CY, Ng WF, Nicholls JM, et al. Re-emergence of fatal human influenza A subtype H5N1 disease. Lancet 2004;363(9409):617-9.
[88] WHO-Map-of-OutbreakArea-20080417. World Health Organization (WHO). Areas reporting confirmed occurrence of H5N1 avian influenza in poultry and wild birds since 2003, status as of 17.04.2008, http://gamapserver.who.int/mapLibrarv/app/searchResults.aspx.
[89] Ducatez MF, Olinger CM, Owoade AA, De Landtsheer S, Ammerlaan W, Niesters HG, et al. Avian flu: multiple introductions of H5N1 in Nigeria. Nature 2006;442(7098):37.
[90] Salzberg SL, Kingsford C, Cattoli G, Spiro DJ, Janies DA, Aly MM, et al. Genome analysis linking recent European and African influenza (H5N1) viruses. Emerg Infect Dis 2007;13(5):713-8.
[91] Butler D. Thai dogs carry bird-flu virus, but will they spread it? Nature 2006;439(7078):773.
[92] Cauthen AN, Swayne DE, Schultz-Cherry S, Perdue ML, Suarez DL. Continued circulation in China of highly pathogenic avian influenza viruses encoding the hemagglutinin gene associated with the 1997 H5N1 outbreak in poultry and humans. J Virol 2000;74(14):6592-9.
[93] Guan Y, Peiris JS, Lipatov AS, Ellis TM, Dyrting KC, Krauss S, et al. Emergence of multiple genotypes of H5N1 avian influenza viruses in Hong Kong SAR. Proc Natl Acad Sci U S A 2002;99(13):8950-5.
[94] Chen H, Deng G, Li Z, Tian G, Li Y, Jiao P, et al. The evolution of H5N1 influenza viruses in ducks in southern China. Proc Natl Acad Sci U S A 2004;101(28): 10452-7.
[95] Smith GJ, Naipospos TS, Nguyen TD, de Jong MD, Vijaykrishna D, Usman TB, et al. Evolution and adaptation of H5N1 influenza virus in avian and human hosts in Indonesia and Vietnam. Virology 2006;350(2):258-68.
[96] Subbarao K, Klimov A, Katz J, Regnery H, Lim W, Hall H, et al. Characterization of an avian influenza A (H5N1) virus isolated from a child with a fatal respiratory illness. Science 1998;279(5349):393-6.
[97] Claas EC, Osterhaus AD, van Beek R, De Jong JC, Rimmelzwaan GF, Senne DA, et al. Human influenza A H5N1 virus related to a highly pathogenic avian influenza virus. Lancet 1998;351(9101):472-7.
[98] Guan Y, Poon LL, Cheung CY, Ellis TM, Lim W, Lipatov AS, et al. H5N1 influenza: a protean pandemic threat. Proc Natl Acad Sci U S A2004;101(21):8156-61.
[99] Harvey R, Martin AC, Zambon M, Barclay WS. Restrictions to the adaptation of influenza a virus h5 hemagglutinin to the human host. J Virol 2004;78(l):502-7.
[100] Gambaryan A, Tuzikov A, Pazynina G, Bovin N, Balish A, Klimov A. Evolution of the receptor binding phenotype of influenza A (H5) viruses. Virology 2006;344(2):432-8.
[101] Marschall J, Hartmann K. Avian influenza A H5N1 infections in cats. J Feline Med Surg 2008;10(4):359-65.
[102] Yuen KY, Chan PK, Peiris M, Tsang DN, Que TL, Shortridge KF, et al. Clinical features and rapid viral diagnosis of human disease associated with avian influenza A H5N1 virus. Lancet 1998;351(9101):467-71.
[103] Chan PK. Outbreak of avian influenza A(H5N1) virus infection in Hong Kong in 1997. Clin Infect Dis 2002;34 Suppl 2:S58-64.
[104] Chotpitayasunondh T, Ungchusak K, Hanshaoworakul W, Chunsuthiwat S, Sawanpanyalert P, Kijphati R, et al. Human disease from influenza A (H5N1), Thailand, 2004. Emerg Infect Dis 2005; 11(2):201-9.
[105] de Jong MD, Hien TT. Avian influenza A (H5N1). J Clin Virol 2006;35(l):2-13.
[106] Thanh TT, Doom HR, de Jong MD. Human H5N1 influenza: Current insight into pathogenesis. Int J Biochem Cell Biol 2008;40(12):2671-4.
[107] To KF, Chan PK, Chan KF, Lee WK, Lam WY, Wong KF, et al. Pathology of fatal human infection associated with avian influenza A H5N1 virus. J Med Virol 2001;63(3):242-6.
[108] Rimmelzwaan GF, van Riel D, Baars M, Bestebroer TM, van Amerongen G, Fouchier RA, et al. Influenza A virus (H5N1) infection in cats causes systemic disease with potential novel routes of virus spread within and between hosts. Am J Pathol 2006;168(l):176-83; quiz 364.
[109] Tanaka H, Park CH, Ninomiya A, Ozaki H, Takada A, Umemura T, et al. Neurotropism of the 1997 Hong Kong H5N1 influenza virus in mice. Vet Microbiol 2003;95(l-2):l-13.
[110] Hien TT, de Jong M, Farrar J. Avian influenza-a challenge to global health care structures. N Engl J Med 2004;351(23):2363-5.
[111] Barry JM. The site of origin of the 1918 influenza pandemic and its public health implications. J Transl Med 2004;2(l):3.
[112] Chan MC, Cheung CY, Chui WH, Tsao SW, Nicholls JM, Chan YO, et al. Proinflammatory cytokine responses induced by influenza A (H5N1) viruses in primary human alveolar and bronchial epithelial cells. Respir Res 2005;6:135.
[113] Cheung CY, Poon LL, Lau AS, Luk W, Lau YL, Shortridge KF, et al. Induction of proinflammatory cytokines in human macrophages by influenza A (H5N1) viruses: a mechanism for the unusual severity of human disease? Lancet 2002;360(9348):1831-7.
[114] Lee DC, Cheung CY, Law AH, Mok CK, Peiris M, Lau AS. p38 mitogen-activated protein kinase-dependent hyperinduction of tumor necrosis factor alpha expression in response to avian influenza virus H5N1. J Virol 2005;79(16):10147-54.
[115] Naeve CW, Hinshaw VS, Webster RG. Mutations in the hemagglutinin receptor-binding site can change the biological properties of an influenza virus. J Virol 1984;51(2):567-9.
[116] Shinya K, Ebina M, Yamada S, Ono M, Kasai N, Kawaoka Y Avian flu: influenza virus receptors in the human airway. Nature 2006;440(7083):435-6.
[117] van Riel D, Munster VJ, de Wit E, Rimmelzwaan GF, Fouchier RA, Osterhaus AD, et al. H5N1 Virus Attachment to Lower Respiratory Tract. Science 2006;312(5772):399.
[118] Nicholls JM, Bourne AJ, Chen H, Guan Y, Peiris JS. Sialic acid receptor detection in the human respiratory tract: evidence for widespread distribution of potential binding sites for human and avian influenza viruses. Respir Res 2007;8:73.
[119] Nicholls JM, Chan MC, Chan WY, Wong HK, Cheung CY, Kwong DL, et al. Tropism of avian influenza A (H5N1) in the upper and lower respiratory tract. Nat Med 2007; 13(2): 147-9.
[120] Chandrasekaran A, Srinivasan A, Raman R, Viswanathan K, Raguram S, Tumpey TM, et al. Glycan topology determines human adaptation of avian H5N1 virus hemagglutinin. Nat Biotechnol 2008;26(l):107-13.
[121] Stevens J, Blixt O, Glaser L, Taubenberger JK, Palese P, Paulson JC, et al. Glycan microarray analysis of the hemagglutinins from modern and pandemic influenza viruses reveals different receptor specificities. J Mol Biol 2006;355(5): 1143-55.
[122] Subbarao EK, London W, Murphy BR. A single amino acid in the PB2 gene of influenza A virus is a determinant of host range. J Virol 1993;67(4):1761-4.
[123] Neumann G, Shinya K, Kawaoka Y. Molecular pathogenesis of H5N1 influenza virus infections. Antivir Ther 2007; 12(4 Pt B):617-26.
[124] Li Z, Chen H, Jiao P, Deng G, Tian G, Li Y, et al. Molecular basis of replication of duck H5N1 influenza viruses in a mammalian mouse model. J Virol 2005;79(18):12058-64.
[125] Gabriel G, Herwig A, Klenk HD. Interaction of polymerase subunit PB2 and NP with importin alphal is a determinant of host range of influenza A virus. PLoS Pathog 2008;4(2):ell.
[126] Salomon R, Franks J, Govorkova EA, Ilyushina NA, Yen HL, Hulse-Post DJ, et al. The polymerase complex genes contribute to the high virulence of the human H5N1 influenza virus isolate A/Vietnam/1203/04. J Exp Med 2006;203(3):689-97.
[127] Coleman JR. The PB1-F2 protein of Influenza A virus: increasing pathogenicity by disrupting alveolar macrophages. Virol J 2007;4:9.
[128] Conenello GM, Zamarin D, Perrone LA, Tumpey T, Palese P. A single mutation in the PBI-F2 of H5N1 (HK/97) and 1918 influenza A viruses contributes to increased virulence. PLoS Pathog 2007;3(10):1414-21.
[129] Long JX, Peng DX, Liu YL, Wu YT, Liu XF. Virulence of H5N1 avian influenza virus enhanced by a 15-nucleotide deletion in the viral nonstructural gene. Virus Genes 2008;36(3):471-8.
[130] Obenauer JC, Denson J, Mehta PK, Su X, Mukatira S, Finkelstein DB, et al. Large-scale sequence analysis of avian influenza isolates. Science 2006;311(5767):1576-80.
[131] Maines TR, Lu XH, Erb SM, Edwards L, Guarner J, Greer PW, et al. Avian influenza (H5N1) viruses isolated from humans in Asia in 2004 exhibit increased virulence in mammals. J Virol 2005;79( 18):11788-800.
[132] Lipatov AS, Kwon YK, Sarmento LV, Lager KM, Spackman E, Suarez DL, et al. Domestic pigs have low susceptibility to H5N1 highly pathogenic avian influenza viruses. PLoS Pathog 2008;4(7):e1000102.
[133] Kalthoff D, Hoffmann B, Harder T, Durban M, Beer M. Experimental infection of cattle with highly pathogenic avian influenza virus (H5N1). Emerg Infect Dis 2008;14(7):1132-4.
[134] Giese M, Harder TC, Teifke JP, Klopfleisch R, Breithaupt A, Mettenleiter TC, et al. Experimental infection and natural contact exposure of dogs with avian influenza virus (H5N1). Emerg Infect Dis 2008;14(2):308-10.
[135] Songserm T, Amonsin A, Jam-on R, Sae-Heng N, Pariyothorn N, Payungporn S, et al. Fatal avian influenza A H5N1 inadog. Emerg Infect Dis 2006; 12(11): 1744-7.
[136] Rimmelzwaan GF, Kuiken T, van Amerongen G, Bestebroer TM, Fouchier RA, Osterhaus AD. Pathogenesis of influenza A (H5N1) virus infection in a primate model. J Virol 2001;75(14):6687-91.
[137] Kuiken T, Rimmelzwaan GF, Van Amerongen G, Osterhaus AD. Pathology of human influenza A (H5N1) virus infection in cynomolgus macaques (Macaca fascicularis). Vet Pathol 2003;40(3):304-10.
[138] Zitzow LA, Rowe T, Morken T, Shieh WJ, Zaki S, Katz JM. Pathogenesis of avian influenza A (H5N1) viruses in ferrets. J Virol 2002;76(9):4420-9.
[139] Govorkova EA, Rehg JE, Krauss S, Yen HL, Guan Y, Peiris M, et al. Lethality to ferrets of H5N1 influenza viruses isolated from humans and poultry in 2004. J Virol 2005;79(4):2191-8.
[140] Lu X, Tumpey TM, Morken T, Zaki SR, Cox NJ, Katz JM. A mouse model for the evaluation of pathogenesis and immunity to influenza A (H5N1) viruses isolated from humans. J Virol 1999;73(7):5903-11.
[141] Lipatov AS, Krauss S, Guan Y, Peiris M, Rehg JE, Perez DR, et al. Neurovirulence in mice of H5N1 influenza virus genotypes isolated from Hong Kong poultry in 2001. J Virol 2003;77(6):3816-23.
[142] Xu T, Qiao J, Zhao L, Wang G, He G, Li K, et al. Acute respiratory distress syndrome induced by avian influenza A (H5N1) virus in mice. Am J Respir Crit Care Med 2006;174(9):1011-7.
[143] Gubareva LV, McCullers JA, Bethell RC, Webster RG. Characterization of influenza A/HongKong/156/97 (H5N1) virus in a mouse model and protective effect of zanamivir on H5N1 infection in mice. J Infect Dis 1998;178(6):1592-6.
[144] Mase M, Tanimura N, Imada T, Okamatsu M, Tsukamoto K, Yamaguchi S. Recent H5N1 avian influenza A virus increases rapidly in virulence to mice after a single passage in mice. J Gen Virol 2006;87(Pt 12):3655-9.
[145] Evseenko VA, Bukin EK, Zaykovskaya AV, Sharshov KA, Ternovoi VA, Ignatyev GM, et al. Experimental infection of H5N1 HPAI in BALB/c mice. Virol J 2007;4:77.
[146] Lipatov AS, Andreansky S, Webby RJ, Hulse DJ, Rehg JE, Krauss S, et al. Pathogenesis of Hong Kong H5N1 influenza virus NS gene reassortants in mice: the role of cytokines and B- and T-cell responses. J Gen Virol 2005;86(Pt 4):1121-30.
[147] Chen H, Bright RA, Subbarao K, Smith C, Cox NJ, Katz JM, et al. Polygenic virulence factors involved in pathogenesis of 1997 Hong Kong H5N1 influenza viruses in mice. Virus Res 2007;128(l-2):159-63.
[148] Thiry E, Zicola A, Addie D, Egberink H, Hartmann K, Lutz H, et al. Highly pathogenic avian influenza H5N1 virus in cats and other carnivores. Vet Microbiol 2007;122( 1 -2):25-31.
[149] Klopfleisch R, Wolf PU, Uhl W, Gerst S, Harder T, Starick E, et al. Distribution of lesions and antigen of highly pathogenic avian influenza virus A/Swan/Germany/R65/06 (H5N1) in domestic cats after presumptive infection by wild birds. Vet Pathol 2007;44(3):261-8.
[150] Ayyalasomayajula S, Delaurentis DA, Moore GE, Glickman LT. A Network Model of H5N1 Avian Influenza Transmission Dynamics in Domestic Cats. Zoonoses Public Health 2008.
[151] Hay AJ, Wolstenholme AJ, Skehel JJ, Smith MH. The molecular basis of the specific anti-influenza action of amantadine. Embo J 1985;4(11):3021-4.
[152] Sugrue RJ, Hay AJ. Structural characteristics of the M2 protein of influenza A viruses: evidence that it forms a tetrameric channel. Virology 1991 ;180(2):617-24.
[153] Bui M, Whittaker G, Helenius A. Effect of Ml protein and low pH on nuclear transport of influenza virus ribonucleoproteins. J Virol 1996;70(12):8391-401.
[154] Stephenson I, Nicholson KG. Influenza: vaccination and treatment. Eur Respir J 2001; 17(6): 1282-93.
[155] Jefferson T, Deeks JJ, Demicheli V, Rivetti D, Rudin M. Amantadine and rimantadine for preventing and treating influenza A in adults. Cochrane Database Syst Rev 2004(3):CD001169.
[156] Van Voris LP, Betts RF, Hayden FG, Christmas WA, Douglas RG, Jr. Successful treatment of naturally occurring influenza A/USSR/77 H1N1. Jama 1981;245(11):1128-31.
[157] Wingfield WL, Pollack D, Grunert RR. Therapeutic efficacy of amantadine HC1 and rimantadine HC1 in naturally occurring influenza A2 respiratory illness in man. N Engl J Med 1969;281(11):579-84.
[158] Smorodintsev AA, Karpuhin GI, Zlydnikov DM, Malyseva AM, Svecova EG, Burov SA, et al. The prophylactic effectiveness of amantadine hydrochloride in an epidemic of Hong Kong influenza in Leningrad in 1969. Bull World Health Organ 1970;42(6):865-72.
[159] Bright RA, Medina MJ, Xu X, Perez-Oronoz G, Wallis TR, Davis XM, et al. Incidence of adamantane resistance among influenza A (H3N2) viruses isolated worldwide from 1994 to 2005: a cause for concern. Lancet 2005;366(9492):1175-81.
[160] Englund JA, Champlin RE, Wyde PR, Kantarjian H, Atmar RL, Tarrand J, et al. Common emergence of amantadine- and rimantadine-resistant influenza A viruses in symptomatic immunocompromised adults. Clin Infect Dis 1998;26(6):1418-24.
[161] Hayden FG, Sperber SJ, Belshe RB, Clover RD, Hay AJ, Pyke S. Recovery of drug-resistant influenza A virus during therapeutic use of rimantadine. Antimicrob Agents Chemother 1991;35(9):1741-7.
[162] Jefferson T, Demicheli V, Rivetti D, Jones M, Di Pietrantonj C, Rivetti A. Antivirals for influenza in healthy adults: systematic review. Lancet 2006;367(9507):303-13.
[163] Cheung CL, Rayner JM, Smith GJ, Wang P, Naipospos TS, Zhang J, et al. Distribution of amantadine-resistant H5N1 avian influenza variants in Asia. J Infect Dis 2006; 193( 12): 1626-9.
[164] Le QM, Kiso M, Someya K, S(?)kai YT, Nguyen TH, Nguyen KH, et al. Avian flu: isolation of drug-resistant H5N1 virus. Nature 2005;437(7062):1108.
[165] Varghese JN, McKimm-Breschkin JL, Caldwell JB, Kortt AA, Colman PM. The structure of the complex between influenza virus neuraminidase and sialic acid, the viral receptor. Proteins 1992;14(3):327-32.
[166] Varghese JN, Epa VC, Colman PM. Three-dimensional structure of the complex of 4-guanidino-Neu5Ac2en and influenza virus neuraminidase. Protein Sci 1995;4(6):1081-7.
[167] McNicholl IR, McNicholl JJ. Neuraminidase inhibitors: zanamivir and oseltamivir. Ann Pharmacother 2001;35(l):57-70.
[168] Hayden FG, Osterhaus AD, Treanor JJ, Fleming DM, Aoki FY, Nicholson KG, et al. Efficacy and safety of the neuraminidase inhibitor zanamivir-in the treatment of influenzavirus infections. GG167 Influenza Study Group. N Engl J Med 1997;337(13):874-80.
[169] Monto AS, Fleming DM, Henry D, de Groot R, Makela M, Klein T, et al. Efficacy and safety of the neuraminidase inhibitor zanamivirin the treatment of influenza A and B virus infections. J Infect Dis 1999;180(2):254-61.
[170] Treanor JJ, Hayden FG, Vrooman PS, Barbarash R, Bettis R, Riff D, et al. Efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza: a randomized controlled trial. US Oral Neuraminidase Study Group. Jama 2000;283(8):1016-24.
[171] Nicholson KG, Aoki FY, Osterhaus AD, Trottier S, Carewicz O, Mercier CH, et al. Efficacy and safety of oseltamivir in treatment of acute influenza: a randomised controlled trial. Neuraminidase Inhibitor Flu Treatment Investigator Group. Lancet 2000;355(9218): 1845-50.
[172] Hedrick JA, Barzilai A, Behre U, Henderson FW, Hammond J, Reilly L, et al. Zanamivir for treatment of symptomatic influenza A and B infection in children five to twelve years of age: a randomized controlled trial. Pediatr Infect Dis J 2000;19(5):410-7.
[173] Cooper NJ, Sutton AJ, Abrams KR, Wailoo A, Turner D, Nicholson KG. Effectiveness of neuraminidase inhibitors in treatment and prevention of influenza A and B: systematic review and meta-analyses of randomised controlled trials. Bmj 2003;326(7401):1235.
[174] Whitley RJ, Hayden FG, Reisinger KS, Young N, Dutkowski R, Ipe D, et al. Oral oseltamivir treatment of influenza in children. Pediatr Infect Dis J 2001;20(2):127-33.
[175] Aoki FY, Macleod MD, Paggiaro P, Carewicz O, El Sawy A, Wat C, et al. Early administration of oral oseltamivir increases the benefits of influenza treatment. J Antimicrob Chemother 2003;51(l):123-9.
[176] Kawai N, Ikematsu H, Iwaki N, Satoh I, Kawashima T, Maeda T, et al. Factors influencing the effectiveness of oseltamivir and amantadine for the treatment of influenza: a multicenter study from Japan of the 2002-2003 influenza season. Clin Infect Dis 2005;40(9):1309-16.
[177] McKimm-Breschkin J, Trivedi T, Hampson A, Hay A, Klimov A, Tashiro M, et al. Neuraminidase sequence analysis and susceptibilities of influenza virus clinical isolates to zanamivir and oseltamivir.Antimicrob Agents Chemother 2003;47(7):2264-72.
[178]Tai CY,Escarpe PA,Sidwell RW,Williams MA,Lew W,Wu H,et al.Characterization of human influenza virus variants selected in vitro in the presence of the neuraminidase inhibitor GS 4071.Antimicrob Agents Chemother 1998;42(12):3234-41.
[179]Carr J,Ives J,Kelly L,Lambkin R,Oxford J,Mendel D,et al.Influenza virus carrying neuraminidase with reduced sensitivity to oseltamivir carboxylate has altered properties in vitro and is compromised for infectivity and replicative ability in vivo.Antiviral Res 2002;54(2):79-88.
[180]Ives JA,Carr JA,Mendel DB,Tai CY,Lambkin R,Kelly L,et al.The H274Y mutation in the influenza A/H1N1 neuraminidase active site following oseltamivir phosphate treatment leave virus severely compromised both in vitro and in vivo.Antiviral Res 2002;55(2):307-17.
[181]Herlocher ML,Truscon R,Elias S,Yen HL,Roberts NA,Ohmit SE,et al.Influenza viruses resistant to the antiviral drug oseltamivir: transmission studies in ferrets.J Infect Dis 2004;190(9):1627-30.
[182]Reed LJ,Muench H.A simple method for estimating fifty percent endpoints .Am J Hygiene 1938;27:493-97.
[183]WHO-Mannual-on-diagnosis-and-surveillance.World Health Organization( WHO).Mannual on animal influenza diagnosis and surveillance,2nd ed World Health Organization.Geneva,Switzerland (2002).http://www.who.int/csr/resources/publications/influenza/en/whocdscsrncs20025rev.pdf.
[184]Hoffmann E,Stech J,Guan Y,Webster RG,Perez DR.Universal primer set for the full-length amplification of all influenza A viruses.Arch Virol 2001;146(12):2275-89.
[185]Hall TA.Bioedit: a user-friendly biological sequence alignment editor and analysis program for Window 95/98/NT.Nucleic Acids Symp Ser 1999;41:95-98.
[186]Kumar S,Tamura K,Nei M.MEGA3: Integrated software for Molecular Evolutionary Genetics Analysis and sequence alignment.Brief Bioinform 2004;5(2):150-63.
[187]Jones RG,Landon J.A protocol for 'enhanced pepsin digestion': a step by step method for obtaining pure antibody fragments in high yield from serum.J Immunol Methods 2003;275(1-2):239-50.
[188]Rowe T,Abernathy RA,Hu-Primmer J,Thompson WW,Lu X,Lim W,et al.Detection of antibody to avian influenza A (H5N 1)virus in human serum by using a combination of serologic assays.J Clin Microbiol 1999;37(4):937-43.
[189]Kaverin NV,Rudneva IA,Ilyushina NA,Varich NL,Lipatov AS,Smirnov YA,et al.Structure of antigenic sites on the haemagglutinin molecule of H5 avian influenza virus and phenotypic variation of escape mutants.J Gen Virol 2002;83(Pt10):2497-505.
[190]Webster RG,Laver WG.Determination of the number of nonoverlapping antigenic areas on Hong Kong (H3N2)influenza virus hemagglutinin with monoclonal antibodies and the selection of variants with potential epidemiological significance.Virology 1980;104(1):139-48.
[191]Bresson JL,Perronne C,Launay O,Gerdil C,Saville M,Wood J,et al.Safety and immunogenicity of an inactivated split-virion influenza A/Vietnam/1194/2004 (H5N 1)vaccine:phase I randomised trial.Lancet 2006;367(9523):1657-64.
[192]Treanor JJ,Campbell JD,Zangwill KM,Rowe T,Wolff M.Safety and immunogenicity of an inactivated subvirion influenzaA(H5N1)vaccine.N Engl J Med 2006;354(13):1343-51.
[193]Smith DJ,Lapedes AS,de Jong JC,Bestebroer TM,Rimmelzwaan GF,Osterhaus AD,et al.Mapping the antigenic and genetic evolution of influenza virus.Science 2004;305(5682):371-6.
[194]陈毅歆,罗海峰,葛胜祥,郭永利.高致病性H5亚型禽流行性感冒病毒血凝素单克隆抗体的制备与初步应用.病毒学报2005;21(6):422-27.
[195]WHO-Antigenic-analysis.World Health Organization(WHO).Antigenic and genetic
characteristics of H5N1 viruses and candidate H5N1 vaccine viruses developed for potential use as human vaccines(September 2008).http://www.who.int/csr/disease/avian_influenza/guidelines/h5n 1 virus/en/index.html.
[196]Simmons CP,Bernasconi NL,Suguitan AL,Mills K,Ward JM,Chau NV,et al.Prophylactic and therapeutic efficacy of human monoclonal antibodies against H5N1 influenza.PLoS Med 2007;4(5):e178.
[197]Markine-Goriaynoff D,Coutelier JP.Increased efficacy of the immunoglobulin G2a subclass in antibody-mediated protection against lactate dehydrogenase-elevating virus-induced polioencephalomyelitis revealed with switch mutants.J Virol 2002;76(1):432-5.
[198]Hessell AJ,Hangartner L,Hunter M,Havenith CE,Beurskens FJ,Bakker JM,et al.Fc receptor but not complement binding is important in antibody protection against HIV.Nature 2007:449(7158):101-4.
[199] Kaverin NV, Rudneva IA, Govorkova EA, Timofeeva TA, Shilov AA, Kochergin-Nikitsky KS, et al. Epitope mapping of the hemagglutinin molecule of a highly pathogenic H5N1 influenza virus by using monoclonal antibodies. J Virol 2007;81(23):12911-7.
[200] Yang ZY, Wei CJ, Kong WP, Wu L, Xu L, Smith DF, et al. Immunization by avian H5 influenza hemagglutinin mutants with altered receptor binding specificity. Science 2007;317(5839):825-8.
[201] WHO-Antigenic-analysis-Vaccine. World Health Organization(WHO). Antigenic and genetic characteristics of H5N1 viruses and candidate H5N1 vaccine viruses developed for potential use as human vaccines (February 2008). http://www.who.int/csr/disease/avian influenza/guidelines/H5 Vaccine VirusUpdate20080214.pdf.
[202] Leroux-Roels I, Borkowski A, Vanwolleghem T, Drame M, Clement F, Hons E, et al. Antigen sparing and cross-reactive immunity with an adjuvanted rH5Nl prototype pandemic influenza vaccine: a randomised controlled trial. Lancet 2007;370(9587):580-9.
[203] Wiley DC, Wilson IA, Skehel JJ. Structural identification of the antibody-binding sites of Hong Kong influenza haemagglutinin and their involvement in antigenic variation. Nature 1981 ;289(5796):373-8.
[204] Skehel JJ, Wiley DC. Receptor binding and membrane fusion in virus entry: the influenza hemagglutinin. Annu Rev Biochem 2000;69:531-69.
[205] Ferguson NM, Galvani AP, Bush RM. Ecological and immunological determinants of influenza evolution. Nature 2003;422(6930):428-33.
[206] Bush RM, Fitch WM, Bender CA, Cox NJ. Positive selection on the H3 hemagglutinin gene of human influenza virus A. Mol Biol Evol 1999;16(ll):1457-65.
[207] Boltz DA, Douangngeun B, Sinthasak S, Phommachanh P, Rolston S, Chen H, et al. H5N1 influenza viruses in Lao People's Democratic Republic. Emerg Infect Dis 2006;12(10):1593-5.
[208] Chutinimitkul S, Songserm T, Amonsin A, Payungporn S, Suwannakarn K, Damrongwatanapokin S, et al. New strain of influenza A virus (H5N1), Thailand. Eme(?)g Infect Dis 2007;13(3):506-7.
[209] Munoz ET, Deem MW. Epitope analysis for influenza vaccine design. Vaccine 2005;23(9):l144-8.
[210] Webster RG, Laver WG, Air GM, Ward C, Gerhard W, van Wyke KL. The mechanism of antigenic drift in influenza viruses: analysis of Hong Kong (H3N2) variants with monoclonal antibodies to the hemagglutinin molecule. Ann N Y Acad Sci 1980;354:142-61.
[211] Hulse-Post DJ, Sturm-Ramirez KM, Humberd J, Seiler P, Govorkova EA, Krauss S, et al. Role of domestic ducks in the propagation and biological evolution of highly pathogenic H5N1 influenza viruses in Asia. Proc Natl Acad Sci U S A 2005;102(30):10682-7.
[212] Ellis TM, Leung CY, Chow MK, Bissett LA, Wong W, Guan Y, et al. Vaccination of chickens against H5N1 avian influenza in the face of an outbreak interrupts virus transmission. Avian Pathol 2004;33(4):405-12.
[213] Shortridge KF. Poultry and the influenza H5N1 outbreak in Hong Kong, 1997: abridged chronology and virus isolation. Vaccine 1999; 17 Suppl 1:S26-9.
[214] Qiao C, Yu K, Jiang Y, Li C, Tian G, Wang X, et al. Development of a recombinant fowlpox virus vector-based vaccine of H5N1 subtype avian influenza. Dev Biol (Basel) 2006;124:127-32.
[215] Lee CW, Senne DA, Suarez DL. Generation of reassortant influenza vaccines by reverse genetics that allows utilization of a DIVA (Differentiating Infected from Vaccinated Animals) strategy for the control of avian influenza. Vaccine 2004;22(23-24):3175-81.
[216] Russell CA, Jones TC, Barr IG, Cox NJ, Garten RJ, Gregory V, et al. The global circulation of seasonal influenza A (H3N2) viruses. Science 2008;320(5874):340-6.
[217] Yen HL, Lipatov AS, Ilyushina NA, Govorkova EA, Franks J, Yilmaz N, et al. Inefficient transmission of H5N1 influenza viruses in a ferret contact model. J Virol 2007;81(13):6890-8.
[218] Lu J, Guo Z, Pan X, Wang G, Zhang D, Li Y, et al. Passive immunotherapy for influenza A H5N1 virus infection with equine hyperimmune globulin F(ab')2 in mice. Respir Res 2006;7:43.
[219] Hanson BJ, Boon AC, Lim AP, Webb A, Ooi EE, Webby RJ. Passive immunoprophylaxis and therapy with humanized monoclonal antibody specific for influenza A H5 hemagglutinin in mice. Respir Res 2006;7:126.
[220] Huber VC, Lynch JM, Bucher DJ, Le J, Metzger DW. Fc receptor-mediated phagocytosis makes a significant contribution to clearance of influenza virus infections. J Immunol 2001;166(12):7381-8.
[221] Jayasekera JP, Moseman EA, Carroll MC. Natural antibody and complement mediate neutralization of influenza virus in the absence of prior immunity. J Virol 2007;81(7):3487-94.
[222] Oei AL, Sweep FC, Massuger LF, Olthaar AJ, Thomas CM. Transient human anti-mouse antibodies (HAMA) interference in CA 125 measurements during monitoring of ovarian cancer patients treated with murine monoclonal antibody.Gynecol Oncol 2008;109(2):199-202.
[223]Azinovic I,DeNardo GL,Lamborn KR,Mirick G,Goldstein D,Bradt BM,et al.Survival benefit associated with human anti-mouse antibody (HAMA)in patients with B-cell malignancies.Cancer Immunol Immunother 2006;55(12):1451-8.
[224]Mirick GR,Bradt BM,Denardo SJ,Denardo GL.A review of human anti-globulin antibody (HAGA,HAMA,HACA,HAHA)responses to monoclonal antibodies.Not four letter words.Q J Nucl Med Mol Imaging 2004;48(4):251-7.
[225]Bleeker WK,Agterberg J,Rigter G,van Rooijen N,Bakker JC.Key role of macrophages in hypotensive side effects of immunoglobulin preparations.Studies in an animal model.Clin Exp Immunol 1989;77(3):338-44.
[226]Jahrling PB,Geisbert J,Swearengen JR,Jaax GP,Lewis T,Huggins JW,et al.Passive immunization of Ebola virus-infected cynomolgus monkeys with immunoglobulin from hyperimmune horses.Arch Virol Suppl 1996;11:135-40.
[227]Satpathy DM,Sahu T,Behera TR.Equine rabies immunoglobulin: a study on its clinical safety.J Indian Med Assoc 2005;103(4):238,41-2.
[228]Chiba T,Yokosuka O,Goto S,Fukai K,Imazeki F,Shishido H,et al.Successful clearance of hepatitis B virus after allogeneic stem cell transplantation: beneficial combination of adoptive immunity transfer and lamivudine.Eur J Haematol 2003;71(3):220-3.
[229]Ferrantelli F,Rasmussen RA,Hofmann-Lehmann R,Xu W,McClure HM,Ruprecht RM.Do not underestimate the power of antibodies--lessons from adoptive transfer of antibodies against HIV.Vaccine 2002;20 Suppl 4:A61-5.
[230]Sawyer LA.Antibodies for the prevention and treatment of viral diseases.Antiviral Res 2000;47(2):57-77.
[231]Wang W,Wang EQ,Balthasar JP.Monoclonal antibody pharmacokinetics and pharmacodynamics.Clin Pharmacol Ther 2008;84(5):548-58.
[232]胡显文.全球生物制药市场与我国的路径选择.中国科技投资2008(1):32-36.
[233]Keller MA,Stiehm ER.Passive immunity in prevention and treatment of infectious diseases.Clin Microbiol Rev 2000;13(4):602-14.
[234]Bayry J,Lacroix-Desmazes S,Kazatchkine MD,Kaveri SV.Intravenous immunoglobulin for infectious diseases: back to the pre-antibiotic and passive prophylaxis era? Trends Pharmacol Sci 2004;25(6):306-10.
[235]Lambkin R,McLain L,Jones SE,Aldridge SL,Dimmock NJ.Neutralization escape mutants of type A influenza virus are readily selected by antisera from mice immunized with whole virus: a possible mechanism for antigenic drift.J Gen Virol 1994;75(Pt 12):3493-502.
[236]Wiley DC,Skehel JJ.The structure and function of the hemagglutinin membrane glycoprotein of influenza virus.Annu Rev Biochem 1987;56:365-94.
[237]Ilyushina N,Rudneva 1,Gambaryan A,Bovin N,Kaverin N.Monoclonal antibodies differentially affect the interaction between the hemagglutinin of H9 influenza virus escape mutants and sialic receptors.Virology 2004;329(1):33-9.
[238]Yamada A,Brown LE,Webster RG.Characterization of H2 influenza virus hemagglutinin with monoclonal antibodies: influence of receptor specificity.Virology 1984;13 8(2):276-86.
[239]Ibricevic A,Pekosz A,Walter MJ,Newby C,Battaile JT,Brown EG,et al.Influenza virus receptor specificity and cell tropism in mouse and human airway epithelial cells.J Virol 2006;80(15):7469-80.
[240]Philpott M,Easterday BC,Hinshaw VS.Neutralizing epitopes of the H5 hemagglutinin from a virulent avian influenza virus and their relationship to pathogenicity.J Virol 1989;63(8):3453-8.
[241]Philpott M,Hioe C,Sheerar M,Hinshaw VS.Hemagglutinin mutations related to attenuation and altered cell tropism of a virulent avian influenza A virus.J Virol 1990;64(6):2941-7.
[242]Hoffmann E,Lipatov AS,Webby RJ,Govorkova EA,Webster RG.Role of specific hemagglutinin amino acids in the immunogemcity and protection of H5N1 influenza virus vaccines.Proc Natl Acad Sci U S A 2005;102(36):12915-20.
[243]Caton AJ,Brownlee GG,Yewdell JW,Gerhard W.The antigenic structure of the influenza virus A/PR/8/34 hemagglutinin (HI subtype).Cell 1982;31(2 Pt 1):417-27.
[244]Horimoto T,Fukuda N,Iwatsuki-Horimoto K,Guan Y,Lim W,Peiris M,et al.Antigenic differences between H5N1 human influenza viruses isolated in 1997 and 2003.J Vet Med Sci 2004;66(3):303-5.
[245]Chen Y,Xu F,Fan X,Luo H,Ge S,Zheng Q,et al.Evaluation of a rapid test for detection of H5N1 avian influenza virus.J Virol Methods 2008;154(1-2):213-5.
[246]葛胜祥,陈毅歆,徐飞海,罗海峰,陈自敏,郭永利,et al.一种新型H5N1禽流感病毒血凝素抗原快速检测试剂的建立.病毒学报2006.
[2] Ligon BL. Avian influenza virus H5N1: a review of its history and information regarding its potential to cause the next pandemic. Semin Pediatr Infect Dis 2005;16(4):326-35.
[3] Peiris JS, de Jong MD, Guan Y. Avian influenza virus (H5N1): a threat to human health. Clin Microbiol Rev 2007;20(2):243-67.
[4] WHO-Cumulative-Number-20080910. World Health Organization (WHO). Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) Reported to WHO, (10 September 2008). http://www.who.mt/csr/disease/avianinfluenza/country/en/index.html.
[5] Leneva IA, Roberts N, Govorkova EA, Goloubeva OG, Webster RG. The neuraminidase inhibitor GS4104 (oseltamivir phosphate) is efficacious against A/Hong Kong/156/97 (H5N1) and A/Hong Kong/1074/99 (H9N2) influenza viruses. Antiviral Res 2000;48(2):101-15.
[6] Gubareva LV, Webster RG, Hayden FG. Comparison of the activities of zanamivir, oseltamivir, and RWJ-270201 against clinical isolates of influenza virus and neuraminidase inhibitor-resistant variants. Antimicrob Agents Chemother 2001 ;45(12):3403-8.
[7] Sugaya N, Mitamura K, Yamazaki M, Tamura D, Ichikawa M, Kimura K, et al. Lower clinical effectiveness of oseltamivir against influenza B contrasted with influenza A infection in children. Clin Infect Dis 2007;44(2):197-202.
[8] Abdel-Ghafar AN, Chotpitayasunondh T, Gao Z, Hayden FG, Nguyen DH, de Jong MD, et al. Update on avian influenza A (H5N1) virus infection in humans. N Engl J Med 2008;358(3):261-73.
[9] Schun(?)mann HJ, Hill SR, Kakad M, Bellamy R, Uyeki TM, Hayden FG, et al. WHO Rapid Advice Guidelines for pharmacological management of sporadic human infection with avian influenza A (H5N1) virus. Lancet Infect Dis 2007;7(l):21-31.
[10] de Jong MD, Tran TT, Truong HK, Vo MH, Smith GJ, Nguyen VC, et al. Oseltamivir resistance during treatment of influenza A (H5N1) infection. N Engl J Med 2005;353(25):2667-72.
[11] Marasco WA, Sui J. The growth and potential of human antiviral monoclonal antibody therapeutics. Nat Biotechnol 2007;25(12):1421-34.
[12] Luke TC, Kilbane EM, Jackson JL, Hoffman SL. Meta-analysis: convalescent blood products for Spanish influenza pneumonia: a future H5N1 treatment? Ann Intern Med 2006;145(8):599-609.
[13] Zhou B, Zhong N, Guan Y. Treatment with convalescent plasma for influenza A (H5N1) infection. N Engl J Med 2007;357(14):1450-1.
[14] Lamb-Krug-FieldsVirology. Lamb RA, Krug RM. Orthomyxoviridae: The viruses and their replication. In: Fields Virology, fourth edition. Knipe DM, Howley PM eds, Lippincott, Philadelphia 2001,pp 1487-1531..
[15] Chen H, Smith GJ, Li KS, Wang J, Fan XH, Rayner JM, et al. Establishment of multiple sublineages of H5N1 influenza virus in Asia: implications for pandemic control. Proc Natl Acad Sci U S A2006;103(8):2845-50.
[16] Smith GJ, Fan XH, Wang J, Li KS, Qin K, Zhang JX, et al. Emergence and predominance of an H5N1 influenza variant in China. Proc Natl Acad Sci U S A 2006; 103(45): 16936-41.
[17] WHO-EID-nomenclature-system. World Health Organization (WHO). Toward a unified nomenclature system for highly pathogenic avian influenza virus (H5N1). Emerg Infect Dis 2008;14(7):el.
[18] Wright-Webster-Fields Virology. Wright PF, Webster RG. Orthomyxoviruses. In: Fields Virology, fourth edition. Knipe DM, Howley PM eds, Lippincott, Philadelphia 2001, pp 1533-1579.
[19] A revision of the system of nomenclature for influenza viruses: a WHO memorandum. Bull World Health Organ 1980;58(4):585-91.
[20] Chen W, Calvo PA, Malide D, Gibbs J, Schubert U, Bacik I, et al. A novel influenza A virus mitochondrial protein that induces cell death. Nat Med 2001;7(12):1306-12.
[21] InfluenzaReport2006. Ortrud Werner and Timm C. Harder. Avian Influenza: Influenza Report 2006. edited by Bernd Sebastian Kamps, Christian Hoffmann, Wolfgang Preiser. Flying Publisher..
[22] Nicholson KG, Wood JM, Zambon M. Influenza. Lancet 2003;362(9397):1733-45.
[23] Stevens J, Corper AL, Basler CF, Taubenberger JK, Palese P, Wilson IA. Structure of the uncleaved human H1 hemagglutinin from the extinct 1918 influenza virus. Science 2004;303(5665):1866-70.
[24] Gamblin SJ, Haire LF, Russell RJ, Stevens DJ, Xiao B, Ha Y, et al. The structure and receptor binding properties of the 1918 influenza hemagglutinin. Science 2004;303(5665):1838-42.
[25] Webster RG, Bean WJ, Gorman OT, Chambers TM, Kawaoka Y. Evolution and ecology of influenza A viruses. Microbiol Rev 1992;56(1):152-79.
[26] Taubenberger JK, Reid AH, Krafft AE, Bijwaard KE, Fanning TG. Initial genetic characterization of the 1918 "Spanish" influenza virus. Science 1997;275(5307):1793-6.
[27] Johnson NP, Mueller J. Updating the accounts: global mortality of the 1918-1920 "Spanish" influenza pandemic. Bull Hist Med 2002;76(l):105-15.
[28] Connor RJ, Kawaoka Y, Webster RG, Paulson JC. Receptor specificity in human, avian, and equine H2 and H3 influenza virus isolates. Virology 1994;205(l):17-23.
[29] Matrosovich MN, Gambaryan AS, Teneberg S, Piskarev VE, Yamnikova SS, Lvov DK, et al. Avian influenza A viruses differ from human viruses by recognition of sialyloligosaccharides and gangliosides and by a higher conservation of the HA receptor-binding site. Virology 1997;233(l):224-34.
[30] Hatta M, Gao P, Halfmann P, Kawaoka Y. Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses. Science 2001;293(5536):1840-2.
[31] Ennis FA, Cruz J, Jameson J, Klein M, Burt D, Thipphawong J. Augmentation of human influenza A virus-specific cytotoxic T lymphocyte memory by influenza vaccine and adjuvanted carriers (ISCOMS). Virology 1999;259(2):256-61.
[32] Brown EG. Influenza virus genetics. Biomed Pharmacother 2000;54(4):196-209.
[33] Seo SH, Hoffmann E, Webster RG Lethal H5N1 influenza viruses escape host anti-viral cytokine responses. Nat Med 2002;8(9):950-4.
[34] Garcia-Sastre A, Egorov A, Matassov D, Brandt S, Levy DE, Durbin JE, et al. Influenza A virus lacking the NS1 gene replicates in interferon-deficient systems. Virology 1998;252(2):324-30.
[35] Nicholson-Textbook-of-Influenza. Nicholson, KG, R. G. Webster, et al. (1998). "Textbook of Influenza." 1st. published by Blackwell Science Ltd.
[36] Frost WH. Statistics of Influenza Morbidity. Public Health Reports 1920;35(l l):584-97.
[37] Simonsen L, Clarke MJ, Schonberger LB, Arden NH, Cox NJ, Fukuda K. Pandemic versus epidemic influenza mortality: a pattern of changing age distribution. J Infect Dis 1998;178(l):53-60.
[38] Horimoto T, Kawaoka Y. Pandemic threat posed by avian influenza A viruses. Clin Microbiol Rev 2001;14(l):129-49.
[39] Taubenberger JK, Reid AH, Lourens RM, Wang R, Jin G, Fanning TG Characterization of the 1918 influenza virus polymerase genes. Nature 2005;437(7060):889-93.
[40] Scholtissek C, Rohde W, Von Hoyningen V, Rott R. On the origin of the human influenza virus subtypes H2N2 and H3N2. Virology 1978;87(l):13-20.
[41] Kawaoka Y, Krauss S, Webster RG. Avian-to-human transmission of the PB1 gene of influenza A viruses in the 1957 and 1968 pandemics. J Virol 1989;63(11):4603-8.
[42] Lupiani B, Reddy SM. The history of avian influenza. Comp Immunol Microbiol Infect Dis 2008.
[43] Alexander DJ. A review of avian influenza in different bird species. Vet Microbiol 2000;74(l-2):3-13.
[44] Klempner MS, Shapiro DS. Crossing the species barrier-one small step to man, one giant leap to mankind. N Engl J Med 2004;350(12):1171-2.
[45] Webster RG, Peiris M, Chen H, Guan Y. H5N1 outbreaks and enzootic influenza. Emerg Infect Dis 2006;12(l):3-8.
[46] Suarez DL. Evolution of avian influenza viruses. Vet Microbiol 2000;74(l -2): 15-27.
[47] Gorman OT, Bean WJ, Kawaoka Y, Webster RG. Evolution of the nucleoprotein gene of influenza A virus. J Virol 1990;64(4):1487-97.
[48] Webster RG, Yakhno M, Hinshaw VS, Bean WJ, Murti KG. Intestinal influenza: replication and characterization of influenza viruses in ducks. Virology 1978;84(2):268-78.
[49] Halvorson DA, Kelleher CJ, Senne DA. Epizootiology of avian influenza: effect of season on incidence in sentinel ducks and domestic turkeys in Minnesota, Appl Environ Microbiol 1985;49(4):914-9.
[50] Sturm-Ramirez KM, Ellis T, Bousfield B, Bissett L, Dyrting K, Rehg JE, et al. Reemerging H5N1 influenza viruses in Hong Kong in 2002 are highly pathogenic to ducks. J Virol 2004;78(9):4892-901.
[51] Stohr K. Avian influenza and pandemics-research needs and opportunities. N Engl J Med 2005;352(4):405-7.
[52] Chen H, Smith GJ, Zhang SY, Qin K, Wang J, Li KS, et al. Avian flu: H5N1 virus outbreak in migratory waterfowl. Nature 2005;436(7048):191-2.
[53] Liu J, Xiao H, Lei F, Zhu Q, Qin K, Zhang XW, et al. Highly pathogenic H5N1 influenza virus infection in migratory birds. Science 2005;309(5738):1206.
[54] Li KS, Xu KM, Peiris JS, Poon LL, Yu KZ, Yuen KY, et al. Characterization of H9 subtype influenza viruses from the ducks of southern China: a candidate for the next influenza pandemic in humans? J Virol 2003;77(12):6988-94.
[55] Ito T, Couceiro JN, Kelm S, Baum LG, Krauss S, Castrucci MR, et al. Molecular basis for the generation in pigs of influenza A viruses with pandemic potential. J Virol 1998;72(9):7367-73.
[56] Claas EC, Kawaoka Y, de Jong JC, Masurel N, Webster RG Infection of children with avian-human reassortant influenza virus from pigs in Europe. Virology 1994;204(l):453-7.
[57] Hinshaw VS, Bean WJ, Jr., Webster RG, Easterday BC. The prevalence of influenza viruses in swine and the antigenic and genetic relatedness of influenza viruses from man and swine. Virology 1978;84(1):51-62.
[58] Yasuda J, Shortridge KF, Shimizu Y, Kida H. Molecular evidence for a role of domestic ducks in the introduction of avian H3 influenza viruses to pigs in southern China, where the A/Hong Kong/68 (H3N2) strain emerged. J Gen Virol 1991;72 (Pt 8):2007-10.
[59] Bean WJ, Schell M, Katz J, Kawaoka Y, Naeve C, Gorman O, et al. Evolution of the H3 influenza virus hemagglutinin from human and nonhuman hosts. J Virol 1992;66(2): 1129-38.
[60] Pensaert M, Ottis K, Vandeputte J, Kaplan MM, Bachmann PA. Evidence for the natural transmission of influenza A virus from wild ducts to swine and its potential importance for man. Bull World Health Organ 1981;59(l):75-8.
[61] Scholtissek C, Burger H, Bachmann PA, Hanno(?)n C. Genetic relatedness of hemagglutinins of the H1 subtype of influenza A viruses isolated from swine and birds. Virology 1983;129(2):521-3.
[62] Guan Y, Shortridge KF, Krauss S, Li PH, Kawaoka Y, Webster RG Emergence of avian H1N1 influenza viruses in pigs in China. J Virol 1996;70(l l):8041-6.
[63] Peiris JS, Guan Y, Markwell D, Ghose P, Webster RG Shortridge KF. Cocirculation of avian H9N2 and contemporary "human" H3N2 influenza A viruses in pigs in southeastern China: potential for genetic reassortment? J Virol 2001 ;75(20):9679-86.
[64] Ninomiya A, Takada A, Okazaki K, Shortridge KF, Kida H. Seroepidemiological evidence of avian H4, H5, and H9 influenza A virus transmission to pigs in southeastern China. Vet Microbiol 2002;88(2):107-14.
[65] Tumova B, Schild GC. Antigenic relationships between type a influenza viruses of human, porcine, equine, and avian origin. Bull World Health Organ 1972;47(4):453-60.
[66] Kawaoka Y, Webster RG. Origin of the hemagglutinin on A/Equine/Johannesburg/86 (H3N8): the first known equine influenza outbreak in South Africa. Arch Virol 1989; 106(1-2): 159-64.
[67] Guo Y, Wang M, Kawaoka Y, Gorman O, Ito T, Saito T, et al. Characterization of a new avian-like influenza A virus from horses in China. Virology 1992;188(l):245-55.
[68] Webster RG Guo YJ. New influenza virus in horses. Nature 1991;351(6327):527.
[69] Wright-FieldVirology. Wright, P. F., G Neumann, et al. (2007). Orthomyxoviruses. Fields Virology. D. M. Knipe and P. M. Howley. Philadelphia, Wolters Kluwer Health/Lippincott Williams & Wilkins. 2.
[70] Webster RG, Hinshaw VS, Bean WJ, Van Wyke KL, Geraci JR, St Aubin DJ, et al. Characterization of an influenza A virus from seals. Virology 1981;113(2):712-24.
[71] Geraci JR, St Aubin DJ, Barker IK, Webster RG, Hinshaw VS, Bean WJ, et al. Mass mortality of harbor seals: pneumonia associated with influenza A virus. Science 1982;215(4536): 1129-31.
[72] Hinshaw VS, Bean WJ, Webster RG, Rehg JE, Fiorelli P, Early G, et al. Are seals frequently infected with avian influenza viruses? J Virol 1984;51(3):863-5.
[73] Nicholson KG, Nguyen-Van-Tam JS, Ahmed AH, Wiselka MJ, Leese J, Ayres J, et al. Randomised placebo-controlled crossover trial on effect of inactivated influenza vaccine on pulmonary function in asthma. Lancet 1998;351(9099):326-31.
[74] Callan RJ, Early G, Kida H, Hinshaw VS. The appearance of H3 influenza viruses in seals. J Gen Virol 1995;76(Pt1):199-203.
[75] Chambers TM, Yamnikova S, Kawaoka Y, Lvov DK, Webster RG. Antigenic and molecular characterization of subtype H13 hemagglutinin of influenza virus. Virology 1989;172(1): 180-8.
[76] Hinshaw VS, Bean WJ, Geraci J, Fiorelli P, Early G, Webster RG. Characterization of two influenza A viruses from a pilot whale. J Virol 1986;58(2):655-6.
[77] Klingeborn B, Englund L, Rott R, Juntti N, Rockborn G. An avian influenza A virus killing a mammalian species-the mink. Brief report. Arch Virol 1985;86(3-4):347-51.
[78] Keawcharoen J, Oraveerakul K, Kuiken T, Fouchier RA, Amonsin A, Payungporn S, et al. Avian influenza H5N1 in tigers and leopards. Emerg Infect Dis 2004;10(12):2189-91.
[79] Quirk M. Zoo tigers succumb to avian influenza. Lancet Infect Dis 2004;4(12):716.
[80] Thanawongnuwech R, Amonsin A, Tantilertcharoen R, Damrongwatanapokin S, Theamboonlers A, Payungporn S, et al. Probable tiger-to-tiger transmission of avian influenza H5N1. Emerg Infect Dis 2005;ll(5):699-701.
[81] Kuiken T, Rimmelzwaan G, van Riel D, van Amerongen G, Baars M, Fouchier R, et al. Avian H5N1 influenza in cats. Science 2004;306(5694):241.
[82] Shortridge KF, Stuart-Harris CH. An influenza epicentre? Lancet 1982;2(8302):812-3.
[83] Shortridge KF, Zhou NN, Guan Y, Gao P, Ito T, Kawaoka Y, et al. Characterization of avian H5N1 influenza viruses from poultry in Hong Kong. Virology 1998;252(2):331-42.
[84] Xu X, Subbarao, Cox NJ, Guo Y. Genetic characterization of the pathogenic influenza A/Goose/Guangdong/1/96 (H5N1) virus: similarity of its hemagglutinin gene to those of H5N1 viruses from the 1997 outbreaks in Hong Kong. Virology 1999;261(1):15-9.
[85] Sims LD, Ellis TM, Liu KK, Dyrting K, Wong H, Peiris M, et al. Avian influenza in Hong Kong 1997-2002. Avian Dis 2003;47(3 Suppl):832-8.
[86] Claas EC, de Jong JC, van Beek R, Rimmelzwaan GF, Osterhaus AD. Human influenza virus A/HongKong/156/97 (H5N1) infection. Vaccine 1998;16(9-10):977-8.
[87] Peiris JS, Yu WC, Leung CW, Cheung CY, Ng WF, Nicholls JM, et al. Re-emergence of fatal human influenza A subtype H5N1 disease. Lancet 2004;363(9409):617-9.
[88] WHO-Map-of-OutbreakArea-20080417. World Health Organization (WHO). Areas reporting confirmed occurrence of H5N1 avian influenza in poultry and wild birds since 2003, status as of 17.04.2008, http://gamapserver.who.int/mapLibrarv/app/searchResults.aspx.
[89] Ducatez MF, Olinger CM, Owoade AA, De Landtsheer S, Ammerlaan W, Niesters HG, et al. Avian flu: multiple introductions of H5N1 in Nigeria. Nature 2006;442(7098):37.
[90] Salzberg SL, Kingsford C, Cattoli G, Spiro DJ, Janies DA, Aly MM, et al. Genome analysis linking recent European and African influenza (H5N1) viruses. Emerg Infect Dis 2007;13(5):713-8.
[91] Butler D. Thai dogs carry bird-flu virus, but will they spread it? Nature 2006;439(7078):773.
[92] Cauthen AN, Swayne DE, Schultz-Cherry S, Perdue ML, Suarez DL. Continued circulation in China of highly pathogenic avian influenza viruses encoding the hemagglutinin gene associated with the 1997 H5N1 outbreak in poultry and humans. J Virol 2000;74(14):6592-9.
[93] Guan Y, Peiris JS, Lipatov AS, Ellis TM, Dyrting KC, Krauss S, et al. Emergence of multiple genotypes of H5N1 avian influenza viruses in Hong Kong SAR. Proc Natl Acad Sci U S A 2002;99(13):8950-5.
[94] Chen H, Deng G, Li Z, Tian G, Li Y, Jiao P, et al. The evolution of H5N1 influenza viruses in ducks in southern China. Proc Natl Acad Sci U S A 2004;101(28): 10452-7.
[95] Smith GJ, Naipospos TS, Nguyen TD, de Jong MD, Vijaykrishna D, Usman TB, et al. Evolution and adaptation of H5N1 influenza virus in avian and human hosts in Indonesia and Vietnam. Virology 2006;350(2):258-68.
[96] Subbarao K, Klimov A, Katz J, Regnery H, Lim W, Hall H, et al. Characterization of an avian influenza A (H5N1) virus isolated from a child with a fatal respiratory illness. Science 1998;279(5349):393-6.
[97] Claas EC, Osterhaus AD, van Beek R, De Jong JC, Rimmelzwaan GF, Senne DA, et al. Human influenza A H5N1 virus related to a highly pathogenic avian influenza virus. Lancet 1998;351(9101):472-7.
[98] Guan Y, Poon LL, Cheung CY, Ellis TM, Lim W, Lipatov AS, et al. H5N1 influenza: a protean pandemic threat. Proc Natl Acad Sci U S A2004;101(21):8156-61.
[99] Harvey R, Martin AC, Zambon M, Barclay WS. Restrictions to the adaptation of influenza a virus h5 hemagglutinin to the human host. J Virol 2004;78(l):502-7.
[100] Gambaryan A, Tuzikov A, Pazynina G, Bovin N, Balish A, Klimov A. Evolution of the receptor binding phenotype of influenza A (H5) viruses. Virology 2006;344(2):432-8.
[101] Marschall J, Hartmann K. Avian influenza A H5N1 infections in cats. J Feline Med Surg 2008;10(4):359-65.
[102] Yuen KY, Chan PK, Peiris M, Tsang DN, Que TL, Shortridge KF, et al. Clinical features and rapid viral diagnosis of human disease associated with avian influenza A H5N1 virus. Lancet 1998;351(9101):467-71.
[103] Chan PK. Outbreak of avian influenza A(H5N1) virus infection in Hong Kong in 1997. Clin Infect Dis 2002;34 Suppl 2:S58-64.
[104] Chotpitayasunondh T, Ungchusak K, Hanshaoworakul W, Chunsuthiwat S, Sawanpanyalert P, Kijphati R, et al. Human disease from influenza A (H5N1), Thailand, 2004. Emerg Infect Dis 2005; 11(2):201-9.
[105] de Jong MD, Hien TT. Avian influenza A (H5N1). J Clin Virol 2006;35(l):2-13.
[106] Thanh TT, Doom HR, de Jong MD. Human H5N1 influenza: Current insight into pathogenesis. Int J Biochem Cell Biol 2008;40(12):2671-4.
[107] To KF, Chan PK, Chan KF, Lee WK, Lam WY, Wong KF, et al. Pathology of fatal human infection associated with avian influenza A H5N1 virus. J Med Virol 2001;63(3):242-6.
[108] Rimmelzwaan GF, van Riel D, Baars M, Bestebroer TM, van Amerongen G, Fouchier RA, et al. Influenza A virus (H5N1) infection in cats causes systemic disease with potential novel routes of virus spread within and between hosts. Am J Pathol 2006;168(l):176-83; quiz 364.
[109] Tanaka H, Park CH, Ninomiya A, Ozaki H, Takada A, Umemura T, et al. Neurotropism of the 1997 Hong Kong H5N1 influenza virus in mice. Vet Microbiol 2003;95(l-2):l-13.
[110] Hien TT, de Jong M, Farrar J. Avian influenza-a challenge to global health care structures. N Engl J Med 2004;351(23):2363-5.
[111] Barry JM. The site of origin of the 1918 influenza pandemic and its public health implications. J Transl Med 2004;2(l):3.
[112] Chan MC, Cheung CY, Chui WH, Tsao SW, Nicholls JM, Chan YO, et al. Proinflammatory cytokine responses induced by influenza A (H5N1) viruses in primary human alveolar and bronchial epithelial cells. Respir Res 2005;6:135.
[113] Cheung CY, Poon LL, Lau AS, Luk W, Lau YL, Shortridge KF, et al. Induction of proinflammatory cytokines in human macrophages by influenza A (H5N1) viruses: a mechanism for the unusual severity of human disease? Lancet 2002;360(9348):1831-7.
[114] Lee DC, Cheung CY, Law AH, Mok CK, Peiris M, Lau AS. p38 mitogen-activated protein kinase-dependent hyperinduction of tumor necrosis factor alpha expression in response to avian influenza virus H5N1. J Virol 2005;79(16):10147-54.
[115] Naeve CW, Hinshaw VS, Webster RG. Mutations in the hemagglutinin receptor-binding site can change the biological properties of an influenza virus. J Virol 1984;51(2):567-9.
[116] Shinya K, Ebina M, Yamada S, Ono M, Kasai N, Kawaoka Y Avian flu: influenza virus receptors in the human airway. Nature 2006;440(7083):435-6.
[117] van Riel D, Munster VJ, de Wit E, Rimmelzwaan GF, Fouchier RA, Osterhaus AD, et al. H5N1 Virus Attachment to Lower Respiratory Tract. Science 2006;312(5772):399.
[118] Nicholls JM, Bourne AJ, Chen H, Guan Y, Peiris JS. Sialic acid receptor detection in the human respiratory tract: evidence for widespread distribution of potential binding sites for human and avian influenza viruses. Respir Res 2007;8:73.
[119] Nicholls JM, Chan MC, Chan WY, Wong HK, Cheung CY, Kwong DL, et al. Tropism of avian influenza A (H5N1) in the upper and lower respiratory tract. Nat Med 2007; 13(2): 147-9.
[120] Chandrasekaran A, Srinivasan A, Raman R, Viswanathan K, Raguram S, Tumpey TM, et al. Glycan topology determines human adaptation of avian H5N1 virus hemagglutinin. Nat Biotechnol 2008;26(l):107-13.
[121] Stevens J, Blixt O, Glaser L, Taubenberger JK, Palese P, Paulson JC, et al. Glycan microarray analysis of the hemagglutinins from modern and pandemic influenza viruses reveals different receptor specificities. J Mol Biol 2006;355(5): 1143-55.
[122] Subbarao EK, London W, Murphy BR. A single amino acid in the PB2 gene of influenza A virus is a determinant of host range. J Virol 1993;67(4):1761-4.
[123] Neumann G, Shinya K, Kawaoka Y. Molecular pathogenesis of H5N1 influenza virus infections. Antivir Ther 2007; 12(4 Pt B):617-26.
[124] Li Z, Chen H, Jiao P, Deng G, Tian G, Li Y, et al. Molecular basis of replication of duck H5N1 influenza viruses in a mammalian mouse model. J Virol 2005;79(18):12058-64.
[125] Gabriel G, Herwig A, Klenk HD. Interaction of polymerase subunit PB2 and NP with importin alphal is a determinant of host range of influenza A virus. PLoS Pathog 2008;4(2):ell.
[126] Salomon R, Franks J, Govorkova EA, Ilyushina NA, Yen HL, Hulse-Post DJ, et al. The polymerase complex genes contribute to the high virulence of the human H5N1 influenza virus isolate A/Vietnam/1203/04. J Exp Med 2006;203(3):689-97.
[127] Coleman JR. The PB1-F2 protein of Influenza A virus: increasing pathogenicity by disrupting alveolar macrophages. Virol J 2007;4:9.
[128] Conenello GM, Zamarin D, Perrone LA, Tumpey T, Palese P. A single mutation in the PBI-F2 of H5N1 (HK/97) and 1918 influenza A viruses contributes to increased virulence. PLoS Pathog 2007;3(10):1414-21.
[129] Long JX, Peng DX, Liu YL, Wu YT, Liu XF. Virulence of H5N1 avian influenza virus enhanced by a 15-nucleotide deletion in the viral nonstructural gene. Virus Genes 2008;36(3):471-8.
[130] Obenauer JC, Denson J, Mehta PK, Su X, Mukatira S, Finkelstein DB, et al. Large-scale sequence analysis of avian influenza isolates. Science 2006;311(5767):1576-80.
[131] Maines TR, Lu XH, Erb SM, Edwards L, Guarner J, Greer PW, et al. Avian influenza (H5N1) viruses isolated from humans in Asia in 2004 exhibit increased virulence in mammals. J Virol 2005;79( 18):11788-800.
[132] Lipatov AS, Kwon YK, Sarmento LV, Lager KM, Spackman E, Suarez DL, et al. Domestic pigs have low susceptibility to H5N1 highly pathogenic avian influenza viruses. PLoS Pathog 2008;4(7):e1000102.
[133] Kalthoff D, Hoffmann B, Harder T, Durban M, Beer M. Experimental infection of cattle with highly pathogenic avian influenza virus (H5N1). Emerg Infect Dis 2008;14(7):1132-4.
[134] Giese M, Harder TC, Teifke JP, Klopfleisch R, Breithaupt A, Mettenleiter TC, et al. Experimental infection and natural contact exposure of dogs with avian influenza virus (H5N1). Emerg Infect Dis 2008;14(2):308-10.
[135] Songserm T, Amonsin A, Jam-on R, Sae-Heng N, Pariyothorn N, Payungporn S, et al. Fatal avian influenza A H5N1 inadog. Emerg Infect Dis 2006; 12(11): 1744-7.
[136] Rimmelzwaan GF, Kuiken T, van Amerongen G, Bestebroer TM, Fouchier RA, Osterhaus AD. Pathogenesis of influenza A (H5N1) virus infection in a primate model. J Virol 2001;75(14):6687-91.
[137] Kuiken T, Rimmelzwaan GF, Van Amerongen G, Osterhaus AD. Pathology of human influenza A (H5N1) virus infection in cynomolgus macaques (Macaca fascicularis). Vet Pathol 2003;40(3):304-10.
[138] Zitzow LA, Rowe T, Morken T, Shieh WJ, Zaki S, Katz JM. Pathogenesis of avian influenza A (H5N1) viruses in ferrets. J Virol 2002;76(9):4420-9.
[139] Govorkova EA, Rehg JE, Krauss S, Yen HL, Guan Y, Peiris M, et al. Lethality to ferrets of H5N1 influenza viruses isolated from humans and poultry in 2004. J Virol 2005;79(4):2191-8.
[140] Lu X, Tumpey TM, Morken T, Zaki SR, Cox NJ, Katz JM. A mouse model for the evaluation of pathogenesis and immunity to influenza A (H5N1) viruses isolated from humans. J Virol 1999;73(7):5903-11.
[141] Lipatov AS, Krauss S, Guan Y, Peiris M, Rehg JE, Perez DR, et al. Neurovirulence in mice of H5N1 influenza virus genotypes isolated from Hong Kong poultry in 2001. J Virol 2003;77(6):3816-23.
[142] Xu T, Qiao J, Zhao L, Wang G, He G, Li K, et al. Acute respiratory distress syndrome induced by avian influenza A (H5N1) virus in mice. Am J Respir Crit Care Med 2006;174(9):1011-7.
[143] Gubareva LV, McCullers JA, Bethell RC, Webster RG. Characterization of influenza A/HongKong/156/97 (H5N1) virus in a mouse model and protective effect of zanamivir on H5N1 infection in mice. J Infect Dis 1998;178(6):1592-6.
[144] Mase M, Tanimura N, Imada T, Okamatsu M, Tsukamoto K, Yamaguchi S. Recent H5N1 avian influenza A virus increases rapidly in virulence to mice after a single passage in mice. J Gen Virol 2006;87(Pt 12):3655-9.
[145] Evseenko VA, Bukin EK, Zaykovskaya AV, Sharshov KA, Ternovoi VA, Ignatyev GM, et al. Experimental infection of H5N1 HPAI in BALB/c mice. Virol J 2007;4:77.
[146] Lipatov AS, Andreansky S, Webby RJ, Hulse DJ, Rehg JE, Krauss S, et al. Pathogenesis of Hong Kong H5N1 influenza virus NS gene reassortants in mice: the role of cytokines and B- and T-cell responses. J Gen Virol 2005;86(Pt 4):1121-30.
[147] Chen H, Bright RA, Subbarao K, Smith C, Cox NJ, Katz JM, et al. Polygenic virulence factors involved in pathogenesis of 1997 Hong Kong H5N1 influenza viruses in mice. Virus Res 2007;128(l-2):159-63.
[148] Thiry E, Zicola A, Addie D, Egberink H, Hartmann K, Lutz H, et al. Highly pathogenic avian influenza H5N1 virus in cats and other carnivores. Vet Microbiol 2007;122( 1 -2):25-31.
[149] Klopfleisch R, Wolf PU, Uhl W, Gerst S, Harder T, Starick E, et al. Distribution of lesions and antigen of highly pathogenic avian influenza virus A/Swan/Germany/R65/06 (H5N1) in domestic cats after presumptive infection by wild birds. Vet Pathol 2007;44(3):261-8.
[150] Ayyalasomayajula S, Delaurentis DA, Moore GE, Glickman LT. A Network Model of H5N1 Avian Influenza Transmission Dynamics in Domestic Cats. Zoonoses Public Health 2008.
[151] Hay AJ, Wolstenholme AJ, Skehel JJ, Smith MH. The molecular basis of the specific anti-influenza action of amantadine. Embo J 1985;4(11):3021-4.
[152] Sugrue RJ, Hay AJ. Structural characteristics of the M2 protein of influenza A viruses: evidence that it forms a tetrameric channel. Virology 1991 ;180(2):617-24.
[153] Bui M, Whittaker G, Helenius A. Effect of Ml protein and low pH on nuclear transport of influenza virus ribonucleoproteins. J Virol 1996;70(12):8391-401.
[154] Stephenson I, Nicholson KG. Influenza: vaccination and treatment. Eur Respir J 2001; 17(6): 1282-93.
[155] Jefferson T, Deeks JJ, Demicheli V, Rivetti D, Rudin M. Amantadine and rimantadine for preventing and treating influenza A in adults. Cochrane Database Syst Rev 2004(3):CD001169.
[156] Van Voris LP, Betts RF, Hayden FG, Christmas WA, Douglas RG, Jr. Successful treatment of naturally occurring influenza A/USSR/77 H1N1. Jama 1981;245(11):1128-31.
[157] Wingfield WL, Pollack D, Grunert RR. Therapeutic efficacy of amantadine HC1 and rimantadine HC1 in naturally occurring influenza A2 respiratory illness in man. N Engl J Med 1969;281(11):579-84.
[158] Smorodintsev AA, Karpuhin GI, Zlydnikov DM, Malyseva AM, Svecova EG, Burov SA, et al. The prophylactic effectiveness of amantadine hydrochloride in an epidemic of Hong Kong influenza in Leningrad in 1969. Bull World Health Organ 1970;42(6):865-72.
[159] Bright RA, Medina MJ, Xu X, Perez-Oronoz G, Wallis TR, Davis XM, et al. Incidence of adamantane resistance among influenza A (H3N2) viruses isolated worldwide from 1994 to 2005: a cause for concern. Lancet 2005;366(9492):1175-81.
[160] Englund JA, Champlin RE, Wyde PR, Kantarjian H, Atmar RL, Tarrand J, et al. Common emergence of amantadine- and rimantadine-resistant influenza A viruses in symptomatic immunocompromised adults. Clin Infect Dis 1998;26(6):1418-24.
[161] Hayden FG, Sperber SJ, Belshe RB, Clover RD, Hay AJ, Pyke S. Recovery of drug-resistant influenza A virus during therapeutic use of rimantadine. Antimicrob Agents Chemother 1991;35(9):1741-7.
[162] Jefferson T, Demicheli V, Rivetti D, Jones M, Di Pietrantonj C, Rivetti A. Antivirals for influenza in healthy adults: systematic review. Lancet 2006;367(9507):303-13.
[163] Cheung CL, Rayner JM, Smith GJ, Wang P, Naipospos TS, Zhang J, et al. Distribution of amantadine-resistant H5N1 avian influenza variants in Asia. J Infect Dis 2006; 193( 12): 1626-9.
[164] Le QM, Kiso M, Someya K, S(?)kai YT, Nguyen TH, Nguyen KH, et al. Avian flu: isolation of drug-resistant H5N1 virus. Nature 2005;437(7062):1108.
[165] Varghese JN, McKimm-Breschkin JL, Caldwell JB, Kortt AA, Colman PM. The structure of the complex between influenza virus neuraminidase and sialic acid, the viral receptor. Proteins 1992;14(3):327-32.
[166] Varghese JN, Epa VC, Colman PM. Three-dimensional structure of the complex of 4-guanidino-Neu5Ac2en and influenza virus neuraminidase. Protein Sci 1995;4(6):1081-7.
[167] McNicholl IR, McNicholl JJ. Neuraminidase inhibitors: zanamivir and oseltamivir. Ann Pharmacother 2001;35(l):57-70.
[168] Hayden FG, Osterhaus AD, Treanor JJ, Fleming DM, Aoki FY, Nicholson KG, et al. Efficacy and safety of the neuraminidase inhibitor zanamivir-in the treatment of influenzavirus infections. GG167 Influenza Study Group. N Engl J Med 1997;337(13):874-80.
[169] Monto AS, Fleming DM, Henry D, de Groot R, Makela M, Klein T, et al. Efficacy and safety of the neuraminidase inhibitor zanamivirin the treatment of influenza A and B virus infections. J Infect Dis 1999;180(2):254-61.
[170] Treanor JJ, Hayden FG, Vrooman PS, Barbarash R, Bettis R, Riff D, et al. Efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza: a randomized controlled trial. US Oral Neuraminidase Study Group. Jama 2000;283(8):1016-24.
[171] Nicholson KG, Aoki FY, Osterhaus AD, Trottier S, Carewicz O, Mercier CH, et al. Efficacy and safety of oseltamivir in treatment of acute influenza: a randomised controlled trial. Neuraminidase Inhibitor Flu Treatment Investigator Group. Lancet 2000;355(9218): 1845-50.
[172] Hedrick JA, Barzilai A, Behre U, Henderson FW, Hammond J, Reilly L, et al. Zanamivir for treatment of symptomatic influenza A and B infection in children five to twelve years of age: a randomized controlled trial. Pediatr Infect Dis J 2000;19(5):410-7.
[173] Cooper NJ, Sutton AJ, Abrams KR, Wailoo A, Turner D, Nicholson KG. Effectiveness of neuraminidase inhibitors in treatment and prevention of influenza A and B: systematic review and meta-analyses of randomised controlled trials. Bmj 2003;326(7401):1235.
[174] Whitley RJ, Hayden FG, Reisinger KS, Young N, Dutkowski R, Ipe D, et al. Oral oseltamivir treatment of influenza in children. Pediatr Infect Dis J 2001;20(2):127-33.
[175] Aoki FY, Macleod MD, Paggiaro P, Carewicz O, El Sawy A, Wat C, et al. Early administration of oral oseltamivir increases the benefits of influenza treatment. J Antimicrob Chemother 2003;51(l):123-9.
[176] Kawai N, Ikematsu H, Iwaki N, Satoh I, Kawashima T, Maeda T, et al. Factors influencing the effectiveness of oseltamivir and amantadine for the treatment of influenza: a multicenter study from Japan of the 2002-2003 influenza season. Clin Infect Dis 2005;40(9):1309-16.
[177] McKimm-Breschkin J, Trivedi T, Hampson A, Hay A, Klimov A, Tashiro M, et al. Neuraminidase sequence analysis and susceptibilities of influenza virus clinical isolates to zanamivir and oseltamivir.Antimicrob Agents Chemother 2003;47(7):2264-72.
[178]Tai CY,Escarpe PA,Sidwell RW,Williams MA,Lew W,Wu H,et al.Characterization of human influenza virus variants selected in vitro in the presence of the neuraminidase inhibitor GS 4071.Antimicrob Agents Chemother 1998;42(12):3234-41.
[179]Carr J,Ives J,Kelly L,Lambkin R,Oxford J,Mendel D,et al.Influenza virus carrying neuraminidase with reduced sensitivity to oseltamivir carboxylate has altered properties in vitro and is compromised for infectivity and replicative ability in vivo.Antiviral Res 2002;54(2):79-88.
[180]Ives JA,Carr JA,Mendel DB,Tai CY,Lambkin R,Kelly L,et al.The H274Y mutation in the influenza A/H1N1 neuraminidase active site following oseltamivir phosphate treatment leave virus severely compromised both in vitro and in vivo.Antiviral Res 2002;55(2):307-17.
[181]Herlocher ML,Truscon R,Elias S,Yen HL,Roberts NA,Ohmit SE,et al.Influenza viruses resistant to the antiviral drug oseltamivir: transmission studies in ferrets.J Infect Dis 2004;190(9):1627-30.
[182]Reed LJ,Muench H.A simple method for estimating fifty percent endpoints .Am J Hygiene 1938;27:493-97.
[183]WHO-Mannual-on-diagnosis-and-surveillance.World Health Organization( WHO).Mannual on animal influenza diagnosis and surveillance,2nd ed World Health Organization.Geneva,Switzerland (2002).http://www.who.int/csr/resources/publications/influenza/en/whocdscsrncs20025rev.pdf.
[184]Hoffmann E,Stech J,Guan Y,Webster RG,Perez DR.Universal primer set for the full-length amplification of all influenza A viruses.Arch Virol 2001;146(12):2275-89.
[185]Hall TA.Bioedit: a user-friendly biological sequence alignment editor and analysis program for Window 95/98/NT.Nucleic Acids Symp Ser 1999;41:95-98.
[186]Kumar S,Tamura K,Nei M.MEGA3: Integrated software for Molecular Evolutionary Genetics Analysis and sequence alignment.Brief Bioinform 2004;5(2):150-63.
[187]Jones RG,Landon J.A protocol for 'enhanced pepsin digestion': a step by step method for obtaining pure antibody fragments in high yield from serum.J Immunol Methods 2003;275(1-2):239-50.
[188]Rowe T,Abernathy RA,Hu-Primmer J,Thompson WW,Lu X,Lim W,et al.Detection of antibody to avian influenza A (H5N 1)virus in human serum by using a combination of serologic assays.J Clin Microbiol 1999;37(4):937-43.
[189]Kaverin NV,Rudneva IA,Ilyushina NA,Varich NL,Lipatov AS,Smirnov YA,et al.Structure of antigenic sites on the haemagglutinin molecule of H5 avian influenza virus and phenotypic variation of escape mutants.J Gen Virol 2002;83(Pt10):2497-505.
[190]Webster RG,Laver WG.Determination of the number of nonoverlapping antigenic areas on Hong Kong (H3N2)influenza virus hemagglutinin with monoclonal antibodies and the selection of variants with potential epidemiological significance.Virology 1980;104(1):139-48.
[191]Bresson JL,Perronne C,Launay O,Gerdil C,Saville M,Wood J,et al.Safety and immunogenicity of an inactivated split-virion influenza A/Vietnam/1194/2004 (H5N 1)vaccine:phase I randomised trial.Lancet 2006;367(9523):1657-64.
[192]Treanor JJ,Campbell JD,Zangwill KM,Rowe T,Wolff M.Safety and immunogenicity of an inactivated subvirion influenzaA(H5N1)vaccine.N Engl J Med 2006;354(13):1343-51.
[193]Smith DJ,Lapedes AS,de Jong JC,Bestebroer TM,Rimmelzwaan GF,Osterhaus AD,et al.Mapping the antigenic and genetic evolution of influenza virus.Science 2004;305(5682):371-6.
[194]陈毅歆,罗海峰,葛胜祥,郭永利.高致病性H5亚型禽流行性感冒病毒血凝素单克隆抗体的制备与初步应用.病毒学报2005;21(6):422-27.
[195]WHO-Antigenic-analysis.World Health Organization(WHO).Antigenic and genetic
characteristics of H5N1 viruses and candidate H5N1 vaccine viruses developed for potential use as human vaccines(September 2008).http://www.who.int/csr/disease/avian_influenza/guidelines/h5n 1 virus/en/index.html.
[196]Simmons CP,Bernasconi NL,Suguitan AL,Mills K,Ward JM,Chau NV,et al.Prophylactic and therapeutic efficacy of human monoclonal antibodies against H5N1 influenza.PLoS Med 2007;4(5):e178.
[197]Markine-Goriaynoff D,Coutelier JP.Increased efficacy of the immunoglobulin G2a subclass in antibody-mediated protection against lactate dehydrogenase-elevating virus-induced polioencephalomyelitis revealed with switch mutants.J Virol 2002;76(1):432-5.
[198]Hessell AJ,Hangartner L,Hunter M,Havenith CE,Beurskens FJ,Bakker JM,et al.Fc receptor but not complement binding is important in antibody protection against HIV.Nature 2007:449(7158):101-4.
[199] Kaverin NV, Rudneva IA, Govorkova EA, Timofeeva TA, Shilov AA, Kochergin-Nikitsky KS, et al. Epitope mapping of the hemagglutinin molecule of a highly pathogenic H5N1 influenza virus by using monoclonal antibodies. J Virol 2007;81(23):12911-7.
[200] Yang ZY, Wei CJ, Kong WP, Wu L, Xu L, Smith DF, et al. Immunization by avian H5 influenza hemagglutinin mutants with altered receptor binding specificity. Science 2007;317(5839):825-8.
[201] WHO-Antigenic-analysis-Vaccine. World Health Organization(WHO). Antigenic and genetic characteristics of H5N1 viruses and candidate H5N1 vaccine viruses developed for potential use as human vaccines (February 2008). http://www.who.int/csr/disease/avian influenza/guidelines/H5 Vaccine VirusUpdate20080214.pdf.
[202] Leroux-Roels I, Borkowski A, Vanwolleghem T, Drame M, Clement F, Hons E, et al. Antigen sparing and cross-reactive immunity with an adjuvanted rH5Nl prototype pandemic influenza vaccine: a randomised controlled trial. Lancet 2007;370(9587):580-9.
[203] Wiley DC, Wilson IA, Skehel JJ. Structural identification of the antibody-binding sites of Hong Kong influenza haemagglutinin and their involvement in antigenic variation. Nature 1981 ;289(5796):373-8.
[204] Skehel JJ, Wiley DC. Receptor binding and membrane fusion in virus entry: the influenza hemagglutinin. Annu Rev Biochem 2000;69:531-69.
[205] Ferguson NM, Galvani AP, Bush RM. Ecological and immunological determinants of influenza evolution. Nature 2003;422(6930):428-33.
[206] Bush RM, Fitch WM, Bender CA, Cox NJ. Positive selection on the H3 hemagglutinin gene of human influenza virus A. Mol Biol Evol 1999;16(ll):1457-65.
[207] Boltz DA, Douangngeun B, Sinthasak S, Phommachanh P, Rolston S, Chen H, et al. H5N1 influenza viruses in Lao People's Democratic Republic. Emerg Infect Dis 2006;12(10):1593-5.
[208] Chutinimitkul S, Songserm T, Amonsin A, Payungporn S, Suwannakarn K, Damrongwatanapokin S, et al. New strain of influenza A virus (H5N1), Thailand. Eme(?)g Infect Dis 2007;13(3):506-7.
[209] Munoz ET, Deem MW. Epitope analysis for influenza vaccine design. Vaccine 2005;23(9):l144-8.
[210] Webster RG, Laver WG, Air GM, Ward C, Gerhard W, van Wyke KL. The mechanism of antigenic drift in influenza viruses: analysis of Hong Kong (H3N2) variants with monoclonal antibodies to the hemagglutinin molecule. Ann N Y Acad Sci 1980;354:142-61.
[211] Hulse-Post DJ, Sturm-Ramirez KM, Humberd J, Seiler P, Govorkova EA, Krauss S, et al. Role of domestic ducks in the propagation and biological evolution of highly pathogenic H5N1 influenza viruses in Asia. Proc Natl Acad Sci U S A 2005;102(30):10682-7.
[212] Ellis TM, Leung CY, Chow MK, Bissett LA, Wong W, Guan Y, et al. Vaccination of chickens against H5N1 avian influenza in the face of an outbreak interrupts virus transmission. Avian Pathol 2004;33(4):405-12.
[213] Shortridge KF. Poultry and the influenza H5N1 outbreak in Hong Kong, 1997: abridged chronology and virus isolation. Vaccine 1999; 17 Suppl 1:S26-9.
[214] Qiao C, Yu K, Jiang Y, Li C, Tian G, Wang X, et al. Development of a recombinant fowlpox virus vector-based vaccine of H5N1 subtype avian influenza. Dev Biol (Basel) 2006;124:127-32.
[215] Lee CW, Senne DA, Suarez DL. Generation of reassortant influenza vaccines by reverse genetics that allows utilization of a DIVA (Differentiating Infected from Vaccinated Animals) strategy for the control of avian influenza. Vaccine 2004;22(23-24):3175-81.
[216] Russell CA, Jones TC, Barr IG, Cox NJ, Garten RJ, Gregory V, et al. The global circulation of seasonal influenza A (H3N2) viruses. Science 2008;320(5874):340-6.
[217] Yen HL, Lipatov AS, Ilyushina NA, Govorkova EA, Franks J, Yilmaz N, et al. Inefficient transmission of H5N1 influenza viruses in a ferret contact model. J Virol 2007;81(13):6890-8.
[218] Lu J, Guo Z, Pan X, Wang G, Zhang D, Li Y, et al. Passive immunotherapy for influenza A H5N1 virus infection with equine hyperimmune globulin F(ab')2 in mice. Respir Res 2006;7:43.
[219] Hanson BJ, Boon AC, Lim AP, Webb A, Ooi EE, Webby RJ. Passive immunoprophylaxis and therapy with humanized monoclonal antibody specific for influenza A H5 hemagglutinin in mice. Respir Res 2006;7:126.
[220] Huber VC, Lynch JM, Bucher DJ, Le J, Metzger DW. Fc receptor-mediated phagocytosis makes a significant contribution to clearance of influenza virus infections. J Immunol 2001;166(12):7381-8.
[221] Jayasekera JP, Moseman EA, Carroll MC. Natural antibody and complement mediate neutralization of influenza virus in the absence of prior immunity. J Virol 2007;81(7):3487-94.
[222] Oei AL, Sweep FC, Massuger LF, Olthaar AJ, Thomas CM. Transient human anti-mouse antibodies (HAMA) interference in CA 125 measurements during monitoring of ovarian cancer patients treated with murine monoclonal antibody.Gynecol Oncol 2008;109(2):199-202.
[223]Azinovic I,DeNardo GL,Lamborn KR,Mirick G,Goldstein D,Bradt BM,et al.Survival benefit associated with human anti-mouse antibody (HAMA)in patients with B-cell malignancies.Cancer Immunol Immunother 2006;55(12):1451-8.
[224]Mirick GR,Bradt BM,Denardo SJ,Denardo GL.A review of human anti-globulin antibody (HAGA,HAMA,HACA,HAHA)responses to monoclonal antibodies.Not four letter words.Q J Nucl Med Mol Imaging 2004;48(4):251-7.
[225]Bleeker WK,Agterberg J,Rigter G,van Rooijen N,Bakker JC.Key role of macrophages in hypotensive side effects of immunoglobulin preparations.Studies in an animal model.Clin Exp Immunol 1989;77(3):338-44.
[226]Jahrling PB,Geisbert J,Swearengen JR,Jaax GP,Lewis T,Huggins JW,et al.Passive immunization of Ebola virus-infected cynomolgus monkeys with immunoglobulin from hyperimmune horses.Arch Virol Suppl 1996;11:135-40.
[227]Satpathy DM,Sahu T,Behera TR.Equine rabies immunoglobulin: a study on its clinical safety.J Indian Med Assoc 2005;103(4):238,41-2.
[228]Chiba T,Yokosuka O,Goto S,Fukai K,Imazeki F,Shishido H,et al.Successful clearance of hepatitis B virus after allogeneic stem cell transplantation: beneficial combination of adoptive immunity transfer and lamivudine.Eur J Haematol 2003;71(3):220-3.
[229]Ferrantelli F,Rasmussen RA,Hofmann-Lehmann R,Xu W,McClure HM,Ruprecht RM.Do not underestimate the power of antibodies--lessons from adoptive transfer of antibodies against HIV.Vaccine 2002;20 Suppl 4:A61-5.
[230]Sawyer LA.Antibodies for the prevention and treatment of viral diseases.Antiviral Res 2000;47(2):57-77.
[231]Wang W,Wang EQ,Balthasar JP.Monoclonal antibody pharmacokinetics and pharmacodynamics.Clin Pharmacol Ther 2008;84(5):548-58.
[232]胡显文.全球生物制药市场与我国的路径选择.中国科技投资2008(1):32-36.
[233]Keller MA,Stiehm ER.Passive immunity in prevention and treatment of infectious diseases.Clin Microbiol Rev 2000;13(4):602-14.
[234]Bayry J,Lacroix-Desmazes S,Kazatchkine MD,Kaveri SV.Intravenous immunoglobulin for infectious diseases: back to the pre-antibiotic and passive prophylaxis era? Trends Pharmacol Sci 2004;25(6):306-10.
[235]Lambkin R,McLain L,Jones SE,Aldridge SL,Dimmock NJ.Neutralization escape mutants of type A influenza virus are readily selected by antisera from mice immunized with whole virus: a possible mechanism for antigenic drift.J Gen Virol 1994;75(Pt 12):3493-502.
[236]Wiley DC,Skehel JJ.The structure and function of the hemagglutinin membrane glycoprotein of influenza virus.Annu Rev Biochem 1987;56:365-94.
[237]Ilyushina N,Rudneva 1,Gambaryan A,Bovin N,Kaverin N.Monoclonal antibodies differentially affect the interaction between the hemagglutinin of H9 influenza virus escape mutants and sialic receptors.Virology 2004;329(1):33-9.
[238]Yamada A,Brown LE,Webster RG.Characterization of H2 influenza virus hemagglutinin with monoclonal antibodies: influence of receptor specificity.Virology 1984;13 8(2):276-86.
[239]Ibricevic A,Pekosz A,Walter MJ,Newby C,Battaile JT,Brown EG,et al.Influenza virus receptor specificity and cell tropism in mouse and human airway epithelial cells.J Virol 2006;80(15):7469-80.
[240]Philpott M,Easterday BC,Hinshaw VS.Neutralizing epitopes of the H5 hemagglutinin from a virulent avian influenza virus and their relationship to pathogenicity.J Virol 1989;63(8):3453-8.
[241]Philpott M,Hioe C,Sheerar M,Hinshaw VS.Hemagglutinin mutations related to attenuation and altered cell tropism of a virulent avian influenza A virus.J Virol 1990;64(6):2941-7.
[242]Hoffmann E,Lipatov AS,Webby RJ,Govorkova EA,Webster RG.Role of specific hemagglutinin amino acids in the immunogemcity and protection of H5N1 influenza virus vaccines.Proc Natl Acad Sci U S A 2005;102(36):12915-20.
[243]Caton AJ,Brownlee GG,Yewdell JW,Gerhard W.The antigenic structure of the influenza virus A/PR/8/34 hemagglutinin (HI subtype).Cell 1982;31(2 Pt 1):417-27.
[244]Horimoto T,Fukuda N,Iwatsuki-Horimoto K,Guan Y,Lim W,Peiris M,et al.Antigenic differences between H5N1 human influenza viruses isolated in 1997 and 2003.J Vet Med Sci 2004;66(3):303-5.
[245]Chen Y,Xu F,Fan X,Luo H,Ge S,Zheng Q,et al.Evaluation of a rapid test for detection of H5N1 avian influenza virus.J Virol Methods 2008;154(1-2):213-5.
[246]葛胜祥,陈毅歆,徐飞海,罗海峰,陈自敏,郭永利,et al.一种新型H5N1禽流感病毒血凝素抗原快速检测试剂的建立.病毒学报2006.