牛病毒性腹泻病毒感染形成和复制的分子机制研究
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摘要
牛病毒性腹泻病（Bovine viral diarrhea, BVD）是由牛病毒性腹泻病毒（Bovine viral diarrheavirus, BVDV）感染引起的，以急慢性粘膜病、持续性感染和免疫抑制为主要特征的传染性疾病；该病被世界动物卫生组织（OIE）列入OIE疾病目录。目前BVDV感染宿主的范围不断扩大，流行趋势呈明显上升状态，给BVD防控计划的实施带来了严重的挑战。
病毒诱导的细胞自噬不仅介导细胞先天性抗病毒免疫反应，也参与病毒抗原的提呈；但很多病毒可演化出不同的机制来破坏、逃避和抑制自噬，甚至利用自噬来增强自身的繁殖。BVDV和宿主蛋白相互作用所导致的细胞损伤是BVDV致病的关键。目前有关BVDV与自噬及宿主蛋白相互作用的报道极为有限。本论文旨在从宿主角度探索BVDV感染复制的相关机制，并取得了如下成果：
1）近几年，我国西北地区流行的BVDV亚型主要是BVDV-1b、BVDV-1d及BVDV-1q。通过RT-PCR方法检测宁夏和青海奶牛血样及牦牛血样中BVDV的感染情况，结果显示BVDV阳性率分别为26.8%和24%。对5′UTR和Npro进行测序和遗传进化分析，证实流行的毒株主要为BVDV-1b、BVDV-1d及BVDV-1q三个亚型。此外，对BVDV抗原阳性的血样进行病毒分离，均为ncp型毒株；电镜和直接免疫荧光检测可观察到细胞中病毒粒子的存在。
2）制备高亲和力的兔抗-Core和兔抗Npro多克隆抗体。构建原核表达载体pET-30a-Core和pET-30a-Npro，转化BL21（DE3），经IPTG诱导、Ni-NTA亲和层析纯化和电洗脱包涵体，获得浓度和纯度较高的Core和Npro重组蛋白，Western-blot检测具有很好的反应原性；利用纯化的蛋白制备兔抗血清，Western-blot和IFA检测表明，两种多克隆抗体均能识别BVDV病毒粒子和细胞中天然表达的Core和Npro蛋白，可用于后续的试验。
3）BVDV感染诱导的细胞自噬促进自身在细胞中的复制。通过透射电镜、Western-blot及荧光显微镜检测，发现BVDV oregon C24V感染MDBK细胞后24h，细胞质中会出现大量的自噬空泡；BVDV感染可引起LC3-Ⅰ向LC3-Ⅱ的转化以及p62的降解；在GFP-LC3质粒转染的细胞，能看到增多的聚集颗粒。用药物抑制细胞自噬或干扰Beclin-1的表达，会降低病毒滴度和病毒蛋白的表达。
4）BVDV Core蛋白与PIAS4蛋白相互作用有利于BVDV的生长和复制。本研究以Core蛋白为诱饵，利用酵母双杂交系统从牛单核细胞文库中筛选出与其相结合的关键宿主蛋白（PIAS4）；通过酵母回交试验和免疫共沉淀试验，证实Core蛋白和PIAS4发生相互作用；激光共聚焦显微镜观察二者在细胞质共定位；下调和上调细胞内PIAS4的表达，病毒滴度和Core蛋白的表达量会发生相应的下降和增加。
本论文研究和发现了宿主细胞内参与BVDV复制的核心元件，为进一步研究自噬和BVDV的互作及BVDV抗宿主免疫应答的机制提供了线索。
Bovine viral diarrhea (BVD) is an important viral disease and listed as a reportable disease of cattleby the World Organization for Animal Health (OIE). BVDV is the causative agent of Bovine viraldiarrhea which causes a series of clinical symptoms of acute or chronic mucosal disease, persistentinfection and immunosuppression. At present, the BVDV prevalence rate is rising in a worldwide andthe host range has expanded, which brings more challenges to prevent and control BVDV infection.
Autophagy is induced by virus infection. It may not only contribute as an intrinsic host defensemechanism against invading viruses but may also mediate antigen presentation, which plays crucial rolein the control of intracellular pathogen. However, many viruses have a number of mechanisms to blockautophagy or even manipulate autophagy for their own benefit. In addition, the interactions betweenBVDV and cellular protein can destroy the normal function of cell and lead to cell damage, which is akey element of causing disease. However, the studies on BVDV-autophagy and BVDV-host interactionsare limited. In order to elucidate the BVDV replication mechanism, the following results were obtained:
1. In recent years, three subgentypes: BVDV-1b, BVDV-1d and BVDV-1q are circulating inWestern China. In order to investigate possible infection in dariy cattle of Ningxia and yaks of Qinghai,all samples were tested for viral nucleic acids by RT-PCR. The results showed the prevalence was26.8%and24%in dariy cattle and yak, respectively. The phylogenetic reconstructions demonstratedthat these samples are BVDV-1, specifically belonging to subgenotypes BVDV-1b, BVDV-1d andBVDV-1q, through the nucleotide analysis of5′UTR and Nproregions. Thirteen viruses were isolatedfrom the antigen-positive samples, and all of them were ncp biotype. Virus particles can be observedunder electron microscopy and direct immunofluorescence.
2. Preparation of high affinity antibodies with Core and Nproproteins. The prokaryotic expressionplasmids pET-30a-Core and pET-30a-Nprowere constructed and transformed into E.coli BL21. Highlypurified Core and Nproproteins were obtained by an affinity chromatography and electroelution afterinduction by IPTG. The western-blot assay indicated that recombinant proteins had good antigenicity.Then, polyclonal antibodies against Core and Nproproteins were prepared. IFA and western-blotexperiments demonstrated that polyclonal antibodies can identify the natural proteins and can be used infollow-up studies.
3. Induction of autophagy can enhance BVDV replication. To determine the role of autophagy inthe infection of BVDV, we performed on MDBK cell infected by BVDV strain Oregon C24V. A largenumber of autophagosome-like double-memberane vesicles in the cytoplasm were observed undertransmission electron microscopy. BVDV infection resulted in conversion of LC3-Ⅰ/Ⅱ, degradation ofp62and the accumulation of GFP-LC3dot. Inhibition of autophagy using wortmannin and smallinterfering RNAs targeting Beclin-1can reduce BVDV replication and expression of Npro.
4. Interaction of cellular PIAS4with BVDV core protein is beneficial to BVDV replication. Usinga yeast two-hybrid screen, the interacting partners of the Core protein were screened in PBMC cDNAlibrary and PIAS4as a novel interacting partner was selected. The interaction between Core and PIAS4 was confirmed by co-immunoprecipitaion and confocal assays. Moreover, Knockdown of PIAS4bysmall interfering RNA resulted in reduction of the virus titer as well as Core protein, whileoverexpression of PIAS4promoted BVDV growth and expression of Core protein.
According to the research, the key host factors that regulate the BVDV replication have beendiscovered, which provide clues for further study on virus-autophagy interaction and mechanism inresistance to host immunity.
病毒诱导的细胞自噬不仅介导细胞先天性抗病毒免疫反应，也参与病毒抗原的提呈；但很多病毒可演化出不同的机制来破坏、逃避和抑制自噬，甚至利用自噬来增强自身的繁殖。BVDV和宿主蛋白相互作用所导致的细胞损伤是BVDV致病的关键。目前有关BVDV与自噬及宿主蛋白相互作用的报道极为有限。本论文旨在从宿主角度探索BVDV感染复制的相关机制，并取得了如下成果：
1）近几年，我国西北地区流行的BVDV亚型主要是BVDV-1b、BVDV-1d及BVDV-1q。通过RT-PCR方法检测宁夏和青海奶牛血样及牦牛血样中BVDV的感染情况，结果显示BVDV阳性率分别为26.8%和24%。对5′UTR和Npro进行测序和遗传进化分析，证实流行的毒株主要为BVDV-1b、BVDV-1d及BVDV-1q三个亚型。此外，对BVDV抗原阳性的血样进行病毒分离，均为ncp型毒株；电镜和直接免疫荧光检测可观察到细胞中病毒粒子的存在。
2）制备高亲和力的兔抗-Core和兔抗Npro多克隆抗体。构建原核表达载体pET-30a-Core和pET-30a-Npro，转化BL21（DE3），经IPTG诱导、Ni-NTA亲和层析纯化和电洗脱包涵体，获得浓度和纯度较高的Core和Npro重组蛋白，Western-blot检测具有很好的反应原性；利用纯化的蛋白制备兔抗血清，Western-blot和IFA检测表明，两种多克隆抗体均能识别BVDV病毒粒子和细胞中天然表达的Core和Npro蛋白，可用于后续的试验。
3）BVDV感染诱导的细胞自噬促进自身在细胞中的复制。通过透射电镜、Western-blot及荧光显微镜检测，发现BVDV oregon C24V感染MDBK细胞后24h，细胞质中会出现大量的自噬空泡；BVDV感染可引起LC3-Ⅰ向LC3-Ⅱ的转化以及p62的降解；在GFP-LC3质粒转染的细胞，能看到增多的聚集颗粒。用药物抑制细胞自噬或干扰Beclin-1的表达，会降低病毒滴度和病毒蛋白的表达。
4）BVDV Core蛋白与PIAS4蛋白相互作用有利于BVDV的生长和复制。本研究以Core蛋白为诱饵，利用酵母双杂交系统从牛单核细胞文库中筛选出与其相结合的关键宿主蛋白（PIAS4）；通过酵母回交试验和免疫共沉淀试验，证实Core蛋白和PIAS4发生相互作用；激光共聚焦显微镜观察二者在细胞质共定位；下调和上调细胞内PIAS4的表达，病毒滴度和Core蛋白的表达量会发生相应的下降和增加。
本论文研究和发现了宿主细胞内参与BVDV复制的核心元件，为进一步研究自噬和BVDV的互作及BVDV抗宿主免疫应答的机制提供了线索。
Bovine viral diarrhea (BVD) is an important viral disease and listed as a reportable disease of cattleby the World Organization for Animal Health (OIE). BVDV is the causative agent of Bovine viraldiarrhea which causes a series of clinical symptoms of acute or chronic mucosal disease, persistentinfection and immunosuppression. At present, the BVDV prevalence rate is rising in a worldwide andthe host range has expanded, which brings more challenges to prevent and control BVDV infection.
Autophagy is induced by virus infection. It may not only contribute as an intrinsic host defensemechanism against invading viruses but may also mediate antigen presentation, which plays crucial rolein the control of intracellular pathogen. However, many viruses have a number of mechanisms to blockautophagy or even manipulate autophagy for their own benefit. In addition, the interactions betweenBVDV and cellular protein can destroy the normal function of cell and lead to cell damage, which is akey element of causing disease. However, the studies on BVDV-autophagy and BVDV-host interactionsare limited. In order to elucidate the BVDV replication mechanism, the following results were obtained:
1. In recent years, three subgentypes: BVDV-1b, BVDV-1d and BVDV-1q are circulating inWestern China. In order to investigate possible infection in dariy cattle of Ningxia and yaks of Qinghai,all samples were tested for viral nucleic acids by RT-PCR. The results showed the prevalence was26.8%and24%in dariy cattle and yak, respectively. The phylogenetic reconstructions demonstratedthat these samples are BVDV-1, specifically belonging to subgenotypes BVDV-1b, BVDV-1d andBVDV-1q, through the nucleotide analysis of5′UTR and Nproregions. Thirteen viruses were isolatedfrom the antigen-positive samples, and all of them were ncp biotype. Virus particles can be observedunder electron microscopy and direct immunofluorescence.
2. Preparation of high affinity antibodies with Core and Nproproteins. The prokaryotic expressionplasmids pET-30a-Core and pET-30a-Nprowere constructed and transformed into E.coli BL21. Highlypurified Core and Nproproteins were obtained by an affinity chromatography and electroelution afterinduction by IPTG. The western-blot assay indicated that recombinant proteins had good antigenicity.Then, polyclonal antibodies against Core and Nproproteins were prepared. IFA and western-blotexperiments demonstrated that polyclonal antibodies can identify the natural proteins and can be used infollow-up studies.
3. Induction of autophagy can enhance BVDV replication. To determine the role of autophagy inthe infection of BVDV, we performed on MDBK cell infected by BVDV strain Oregon C24V. A largenumber of autophagosome-like double-memberane vesicles in the cytoplasm were observed undertransmission electron microscopy. BVDV infection resulted in conversion of LC3-Ⅰ/Ⅱ, degradation ofp62and the accumulation of GFP-LC3dot. Inhibition of autophagy using wortmannin and smallinterfering RNAs targeting Beclin-1can reduce BVDV replication and expression of Npro.
4. Interaction of cellular PIAS4with BVDV core protein is beneficial to BVDV replication. Usinga yeast two-hybrid screen, the interacting partners of the Core protein were screened in PBMC cDNAlibrary and PIAS4as a novel interacting partner was selected. The interaction between Core and PIAS4 was confirmed by co-immunoprecipitaion and confocal assays. Moreover, Knockdown of PIAS4bysmall interfering RNA resulted in reduction of the virus titer as well as Core protein, whileoverexpression of PIAS4promoted BVDV growth and expression of Core protein.
According to the research, the key host factors that regulate the BVDV replication have beendiscovered, which provide clues for further study on virus-autophagy interaction and mechanism inresistance to host immunity.
引文
1.程勇前，等.HCV NS4A与钙离子信号调节亲环素配体相互作用对细胞基因表达的影响[J].中华实验和临床感染病杂志，2008，2（3）：138-144.
2.贺生录，等.牛病毒性腹泻/粘膜病流行情况调查[J].青海畜牧兽医杂志，1991，1：17.
3.韩志辉，等.牦牛病毒性腹泻/粘膜病和传染性鼻气管炎血清学调查[J].中国动物传染病学报，2010，18（6）：56-59.
4.李佑民，等.牛病毒性腹泻-粘膜病病毒（长春184）的分离与鉴定[J].中国人民解放军兽医大学学报，1983，3（2）：113-120.
5.任敏.基因2型牛病毒性腹泻病毒的分离、鉴定[硕士学位论文]乌鲁木齐：新疆农业大学，2007
6.任敏，等.基因2型牛病毒性腹泻病毒新疆及山东分离株的鉴定[J].中国动物传染病学报，2009，17（4）：20-24.
7.沈艳丽，等.青海省玉树地区牛病毒性腹泻-粘膜病血清学调查[J].中国动物检疫，2011，28（10）：52.
8.宋永峰，等.猪源牛病毒性腹泻病毒的流行初探[J].中国动物检疫，2008（7）：25-27.
9.王新平，等.从疑似猪瘟病料中检出牛病毒性腹泻病毒[J].中国兽医学报，1996b，16（4）：341-345.
10.王新平，等.牛病毒性腹泻病毒P125基因重要区的比较与分析[J].中国兽医学报，1996a，16（6）：546-553.
11. Agnello V., et al. Hepatitis C virus and other flaviviridae viruses enter cells via low densitylipoprotein receptor. Proceedings of the National Academy of Sciences1999,96:12766-12771.
12. Aguirre I., et al. Antigenic variability in bovine viral diarrhea virus （BVDV） isolates from alpaca（Vicugna pacos）, llama（Lama glama）and bovines in Chile. Veterinary Microbiology2014,168:324-330.
13. Akira S., et al. Pathogen recognition and innate immunity. Cell2006,124:783-801.
14. Archambault D., et al. Clinical response and immunomodulation following experimental challengeof calves with type2noncytopathogenic bovine viral diarrhea virus. Veterinary Research2000,31:215-227.
15. Arora T., et al. PIASx is a transcriptional co-repressor of signal transducer and activator oftranscription4. Journal of Biological Chemistry2003,278:21327-21330.
16. Atluru D., et al. Suppression of in vitro immunoglobulin biosynthesis in bovine spleen cells bybovine viral diarrhea virus. Clinical Immunology and Immunopathology1979,13:254-260.
17. Baigent S.J., et al. Differential activation of interferon regulatory factors-3and-7bynon-cytopathogenic and cytopathogenic bovine viral diarrhoea virus. Veterinary Immunology andImmunopathology2004,100:135-144.
18. Baker J.C. The clinical manifestations of bovine viral diarrhea infection. The Veterinary clinics ofNorth America. Food Animal Practice1995,11:425.
19. Bauhofer O., et al. Classical swine fever virus Npro interacts with interferon regulatory factor3andinduces its proteasomal degradation. Journal of Virology2007,81:3087-3096.
20. Becher P., et al. Genetic diversity of pestiviruses: identification of novel groups and implications forclassification. Virology1999,262:64-71.
21. Bhatia S., et al. Development and evaluation of a MAb based competitive-ELISA using helicasedomain of NS3protein for sero-diagnosis of bovine viral diarrhea in cattle and buffaloes. Researchin Veterinary Science2008,85:39-45.
22. Bhudevi B., et al. Fluorogenic RT–PCR assay（TaqMan） for detection and classification of bovineviral diarrhea virus. Veterinary Microbiology2001,83:1-10.
23. Bhudevi B., et al. Detection of bovine viral diarrhea virus in formalin fixed paraffin embeddedtissue sections by real time RT-PCR （Taqman）. Journal of virological methods2003,109:25-30.
24. Biuk-Rudan N., et al. Prevalence of antibodies to IBR and BVD viruses in dairy cows withreproductive disorders. Theriogenology1999,51:875-881.
25. Booth R.E., et al. A phylogenetic analysis of Bovine Viral Diarrhoea Virus （BVDV） isolates fromsix different regions of the UK and links to animal movement data. Veterinary Research2013,44:
43.
26. Branza-Nichita N., et al. Antiviral Effect ofN-Butyldeoxynojirimycin against Bovine Viral DiarrheaVirus Correlates with Misfolding of E2Envelope Proteins and Impairment of Their Association intoE1-E2Heterodimers. Journal of Virology2001,75:3527-3536.
27. Brodersen B., et al. Effect of concurrent experimentally induced bovine respiratory syncytial virusand bovine viral diarrhea virus infection on respiratory tract and enteric diseases in calves.American journal of Veterinary Research1998,59:1423-1430.
28. Brodersen B.W., et al. Alteration of leukocyte populations in calves concurrently infected withbovine respiratory syncytial virus and bovine viral diarrhea virus. Viral Immunology1999,12:323-334.
29. Brownlie J., et al. Maternal recognition of foetal infection with bovine virus diarrhoea virus（BVDV）—the bovine pestivirus. Clinical and Diagnostic Virology1998,10:141-150.
30. Buckingham E.M., et al. Autophagy and the effects of its inhibition on varicella-zoster virusglycoprotein biosynthesis and infectivity. Journal of Virology2014,88:890-902.
31. Byers S.R., et al. Disseminated bovine viral diarrhea virus in a persistently infected alpaca（Vicugna pacos） cria. Journal of Veterinary Diagnostic Investigation2009,21:145-148.
32. Carman S., et al. Bovine viral diarrhea virus in alpaca: abortion and persistent infection. Journal ofVeterinary Diagnostic Investigation2005,17:589-593.
33. Charleston B., et al. Masking of two in vitro immunological assays for Mycobacterium bovis（BCG） in calves acutely infected with non-qctopathic bovine viral diarrhoea virus. VeterinaryRecord2001,149:481-484.
34. Chase C.C. The impact of BVDV infection on adaptive immunity. Biologicals: Journal of theInternational Association of Biological Standardization2013,41:52-60.
35. Chase C.C., et al. The immune response to bovine viral diarrhea virus: a constantlychanging picture.Veterinary Clinics of North America: Food Animal Practice2004,20:95-114.
36. Chaumorcel M., et al. Human cytomegalovirus controls a new autophagy-dependent cellularantiviral defense mechanism. Autophagy2008,4:46-53.
37. Chen Q., et al. Induction of autophagy enhances porcine reproductive and respiratory syndromevirus replication. Virus Research2012,163:650-655.
38. Chung C.D., et al. Specific inhibition of Stat3signal transduction by PIAS3. Science1997,278:1803-1805.
39. Cleveland S.M., et al. Assessment of a bovine viral diarrhea virus antigen capture ELISA and amicrotiter virus isolation ELISA using pooled ear notch and serum samples. Journal of VeterinaryDiagnostic Investigation2006,18:395-398.
40. Collen T., et al. Analysis of the repertoire of cattle CD4（+） T cells reactive with bovine viraldiarrhoea virus. Veterinary Immunology and Immunopathology2002a,87:235-238.
41. Collins M.E., et al. Infectivity of pestivirus following persistence of acute infection. VeterinaryMicrobiology2009,138:289-296.
42. Cornish T.E., et al. Comparison of ear notch immunohistochemistry, ear notch antigen-captureELISA, and buffy coat virus isolation for detection of calves persistently infected with bovine viraldiarrhea virus. Journal of Veterinary Diagnostic Investigation2005,17:110-117.
43. Cortez A., et al. Genetic characterization of Brazilian bovine viral diarrhea virus isolates by partialnucleotide sequencing of the5'-UTR region. Pesquisa Veterinária Brasileira2006,26:211-216.
44. Cowley D.B., et al. Bovine viral diarrhoea virus seroprevalence and vaccination usage in dairy andbeef herds in the Republic of Ireland. Irish Veterinary Journal2012,65:1-9.
45. Decaro N., et al. Atypical pestivirus and severe respiratory disease in calves, Europe. EmergingInfectious Diseases2011,17:1549.
46. Deng Y., et al. High prevalence of bovine viral diarrhea virus1in Chinese swine herds. VeterinaryMicrobiology2012,159:490-493.
47. Driskell E.A., et al. A survey of bovine viral diarrhea virus testing in diagnostic laboratories in theUnited States from2004to2005. Journal of Veterinary Diagnostic Investigation2006,18:600-605.
48. Eiras C., et al. Bovine viral diarrhea virus Correlation between herd seroprevalence and bulk tankmilk antibody levels using4commercial immunoassays. Journal of Veterinary DiagnosticInvestigation2012,24:549-553.
49. Eisen-Vandervelde A.L., et al. Hepatitis C virus core selectively suppresses interleukin-12synthesisin human macrophages by interfering with AP-1activation. Journal of Biological Chemistry2004,279:43479-43486.
50. Elahi S.M., et al. Induction of humoral and cellular immune responses against the nucleocapsid ofbovine viral diarrhea virus by an adenovirus vector with an inducible promoter. Virology1999,261:1-7.
51. Ellis J., et al. Effect of maternal antibodies on induction and persistence of vaccine-induced immuneresponses against bovine viral diarrhea virus type II in young calves. Journal of The AmericanVeterinary Medical Association2001,219:351-356.
52. Endsley J.J., et al. Maternal antibody blocks humoral but not T cell responses to BVDV.Biologicals: journal of the International Association of Biological Standardization2003,31:123-125.
53. Falcone E., et al. Genetic heterogeneity of bovine viral diarrhoea virus in Italy. Veterinary ResearchCommunications,2003,27:485-494.
54. Fields S., et al. A novel genetic system to detect protein protein interactions.1989.
55. Fliss P.M., et al. Viral mediated redirection of NEMO/IKKγ to autophagosomes curtails theinflammatory cascade. PLoS Pathogens2012,8: e1002517.
56. Flores E.F., et al. Phylogenetic analysis of Brazilian bovine viral diarrhea virus type2（BVDV-2）isolates: evidence for a subgenotype within BVDV-2. Virus Research2002,87:51-60.
57. Foster A., et al. Bovine viral diarrhoea virus infection of alpacas （Vicugna pacos） in the UK.Veterinary Record2007,161:94-99.
58. Fredriksen B., et al. Level and duration of serum antibodies in cattle infected experimentally andnaturally with bovine virus diarrhoea virus. Veterinary Record1999,144:111-114.
59. Fulton R.W., et al. Bovine viral diarrhea virus （BVDV）1b: predominant BVDV subtype in calveswith respiratory disease. Canadian Journal of Veterinary Research2002,66:181.
60. Fulton R.W., et al. Prevalence of bovine viral diarrhea virus （BVDV） in persistently infectedcattle and BVDV subtypes in affected cattle in beef herds in south central United States. CanadianJournal of Veterinary Research2009,73:283.
61. Fux R., et al. Transient elimination of circulating bovine viral diarrhea virus by colostral antibodiesin persistently infected calves: a pitfall for BVDV-eradication programs? Veterinary Microbiology.2012,161:13-19.
62. Gamlen T., et al. Expression of the NS3protease of cytopathogenic bovine viral diarrhea virusresults in the induction of apoptosis but does not block activation of the beta interferon promoter.Journal of General Virology2010,91:133-144.
63. Gannagé M., et al. Matrix protein2of influenza A virus blocks autophagosome fusion withlysosomes. Cell Host&Microbe2009,6:367-380.
64. Gao J., et al. Seroprevalence of bovine viral diarrhea infection in Yaks （Bos grunniens） on theQinghai-Tibetan Plateau of China. Tropical Animal Health and Production2013a,45:791-793.
65. Gao S., et al. Serological and molecular evidence for natural infection of Bactrian camels withmultiple subgenotypes of bovine viral diarrhea virus in Western China. Veterinary Microbiology2013b,163:172-176.
66. Gao Y., et al. Isolation and identification of a bovine viral diarrhea virus from sika deer in china.Virology Journal2011,8:83.
67. Gil L.H., et al. The amino-terminal domain of bovine viral diarrhea virus Npro protein is necessaryfor alpha/beta interferon antagonism. Journal of Virology2006,80:900-911.
68. Gladue D., et al. Interaction between Core protein of classical swine fever virus with cellularIQGAP1protein appears essential for virulence in swine. Virology2011,412:68-74.
69. Gladue D.P., et al. Effects of the interactions of classical swine fever virus Core protein withproteins of the SUMOylation pathway on virulence in swine. Virology2010,407:129-136.
70. Glew E.J., et al. Antigen-presenting cells from calves persistently infected with bovine viraldiarrhoea virus, a member of the Flaviviridae, are not compromised in their ability to present viralantigen. Journal of General Virology2001,82:1677-1685.
71. Gong X., et al. Identification and characterization of a novel subgenotype of bovine viral diarrheavirus isolated from dairy cattle in Northwestern China. Virus Genes,2013,46:375-376
72. Goyal S.M., et al. Bovine viral diarrhea virus: diagnosis, management, and control.2008.
73. Grégoire I.P., et al. IRGM is a common target of RNA viruses that subvert the autophagy network.PLoS Pathogens2011,7: e1002422.
74. Grummer B., et al. Localization of viral proteins in cells infected with bovine viral diarrhoea virus.The Journal of General Virology2001,82:2597-2605.
75. Hansen T.H., et al. MHC class I antigen presentation: learning from viral evasion strategies. NatureReviews Immunology2009,9:503-513.
76. Hansen T.R., et al. Maternal and Fetal Response to Fetal Persistent Infection with Bovine ViralDiarrhea Virus*. American Journal of Reproductive Immunology2010,64:295-306.
77. Hara H., et al. Involvement of creatine kinase B in hepatitis C virus genome replication throughinteraction with the viral NS4A protein. Journal of Virology2009,83:5137-5147.
78. Hengel H., et al. Viruses know it all: new insights into IFN networks. Trends in Immunology2005,26:396-401.
79. Hiscott J., et al. Hostile takeovers: viral appropriation of the NF-kB pathway. Journal of ClinicalInvestigation2001,107:143-151.
80. Hiscott J., et al. MasterCARD: a priceless link to innate immunity. Trends in Molecular Medicine2006,12:53-56.
81. Horscroft N., et al. Establishment of a subgenomic replicon for bovine viral diarrhea virus in Huh-7cells and modulation of interferon-regulated factor3-mediated antiviral response. Journal ofVirology2005,79:2788-2796.
82. Houe H. Economic impact of BVDV infection in dairies. Biologicals: journal of the InternationalAssociation of Biological Standardization2003,31:137-143.
83. Houe H., et al. Test strategies in bovine viral diarrhea virus control and eradication campaigns inEurope. Journal of Veterinary Diagnostic Investigation2006,18:427-436.
84. Hulst M., et al. Passage of classical swine fever virus in cultured swine kidney cells selects virusvariants that bind to heparan sulfate due to a single amino acid change in envelope protein Erns.Journal of Virology,2000,74:9553-9561.
85. Hwang E.J., et al. SUMOylation of RORα potentiates transcriptional activation function.Biochemical and Biophysical Research Communications2009,378:513-517.
86. Iqbal M., et al. Interactions of bovine viral diarrhoea virus glycoprotein Erns with cell surfaceglycosaminoglycans. Journal of General Virology2000,81:451-459.
87. Itsui Y., et al. Antiviral effects of the interferon‐induced protein guanylate binding protein1and itsinteraction with the hepatitis C virus NS5B protein. Hepatology2009,50:1727-1737.
88. Jackova A., et al. The extended genetic diversity of BVDV-1: typing of BVDV isolates from France.Veterinary Research Communications2008,32:7-11.
89. Johns H.L., et al. The classical swine fever virus N-terminal protease Npro binds to cellular HAX-1.Journal of General Virology2010,91:2677-2686.
90. Johnson C.M., et al. The NS5A protein of bovine viral diarrhoea virus interacts with the alphasubunit of translation elongation factor-1. The Journal of General Virology2001,82:2935-2943.
91. Jones L.R., et al. Application of single-strand conformation polymorphism to the study of bovineviral diarrhea virus isolates. Journal of Veterinary Diagnostic Investigation: official publication ofthe American Association of Veterinary Laboratory Diagnosticians, Inc2001,13:50-56.
92. Jones L.R., et al. Genetic typing of bovine viral diarrhea virus isolates from Argentina. VeterinaryMicrobiology2001,81:367-375.
93. Jounai N., et al. The Atg5–Atg12conjugate associates with innate antiviral immune responses.Proceedings of the National Academy of Sciences2007,104:14050-14055.
94. Kabeya Y., et al. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosomemembranes after processing. The EMBO Journal2000,19:5720-5728.
95. Kadir Y., et al. Genetic heterogeneity of bovine viral diarrhoea virus （BVDV） isolates fromTurkey: identification of a new subgroup in BVDV-1. Veterinary Microbiology2008,130:258-267.
96. Kampa J., et al. Bovine herpesvirus type1（BHV-1） and bovine viral diarrhoea virus （BVDV）infections in dairy herds: self clearance and the detection of seroconversions against a new atypicalpestivirus. The Veterinary Journal2009,182:223-230.
97. Kato H., et al. Differential roles of MDA5and RIG-I helicases in the recognition of RNA viruses.Nature2006,441:101-105.
98. Kawai T., et al. Innate immune recognition of viral infection. Nature Immunology2006,7:131-137.
99. Kennedy J.A. Diagnostic efficacy of a reverse transcriptase–polymerase chain reaction assay toscreen cattle for persistent bovine viral diarrhea virus infection. Journal of the American VeterinaryMedical Association2006,229:1472-1474.
100. Khan F., et al. Evaluation of the effects of long-term storage of bovine ear notch samples on theability of2diagnostic assays to identify calves persistently infected with bovine viral diarrhoeavirus. Journal of the South African Veterinary Association2011,82:18-23.
101. Kihara A., et al. Beclin–phosphatidylinositol3-kinase complex functions at the trans-Golginetwork. EMBO reports2001,2:330-335.
102. Kim S.G., et al. A novel simple one-step single-tube RT-duplex PCR method with an internalcontrol for detection of bovine viral diarrhoea virus in bulk milk, blood, and follicular fluid samples.Biologicals: Journal of the International Association of Biological Standardization2003,31:103-106.
103. Kirkegaard K. Subversion of the cellular autophagy pathway by viruses. Infection and Immunity2009, Springer:323-333.
104. Klionsky D.J. Autophagy: from phenomenology to molecular understanding in less than a decade.Nature Reviews Molecular Cell Biology2007,8:931-937.
105. Klionsky D.J., et al. A unified nomenclature for yeast autophagy-related genes. DevelopmentalCell2003,5:539-545.
106. KLIU INSKAS R., et al. Detection of bovine viral diarrhoea virus in saliva samples. Bull Vet InstPulawy2008,52:31-37.
107. Knight Z., et al. Chemically targeting the PI3K family. Biochemical Society Transactions2007,35:245-249.
108. Kroemer G., et al. Autophagy and the integrated stress response. Molecular Cell2010,40:280-293.
109. Kubota T., et al. PIASy inhibits virus-induced and interferon-stimulated transcription throughdistinct mechanisms. Journal of Biological Chemistry2011,286:8165-8175.
110. Kuhne S., et al. Detection of bovine viral diarrhoea virus infected cattle–testing tissue samplesderived from ear tagging using an Erns capture ELISA. Journal of Veterinary Medicine, Series B2005,52:272-277.
111. Kuta A., et al. Predominance of bovine viral diarrhea virus1b and1d subtypes during eight yearsof survey in Poland. Veterinary Microbiology2013,166:639-644.
112. La Rocca S.A., et al. Loss of interferon regulatory factor3in cells infected with classical swinefever virus involves the N-terminal protease, Npro. Journal of Virology2005,79:7239-7247.
113. Lai M., et al. Hepatitis C virus core protein: possible roles in viral pathogenesis. The Hepatitis CViruses.2000, Springer:117-134.
114. Lambot M., et al. Characterization of the immune response of cattle against non-cytopathic andcytopathic biotypes of bovine viral diarrhoea virus. Journal of General Virology1997,78:1041-1047.
115. Lambot M., et al. Evidence for biotype-specific effects of bovine viral diarrhoea virus on biologicalresponses in acutely infected calves. Journal of General Virology1998,79:27-30.
116. Lan S.Y., et al. Direct interaction between alpha-actinin and hepatitis C virus NS5B. Febs Lett2003,554:289-294.
117. Lanyon S.R., et al. Bovine viral diarrhoea: Pathogenesis and diagnosis. Veterinary Journal.2013.
118. Lee H.K., et al. Autophagy-dependent viral recognition by plasmacytoid dendritic cells. Science2007,315:1398-1401.
119. Lee S.R., et al. Bovine viral diarrhea viruses modulate toll-like receptors, cytokines andco-stimulatory molecules genes expression in bovine peripheral blood monocytes. ComparativeImmunology, Microbiology and Infectious Diseases2008a,31:403-418.
120. Lee Y.R., et al. Autophagic machinery activated by dengue virus enhances virus replication.Virology2008b,374:240-248.
121. Leib D.A., et al. Interaction of ICP34.5with Beclin1modulates herpes simplex virus type1pathogenesis through control of CD4+T-cell responses. Journal of Virology2009,83:12164-12171.
122. Letellier C., et al. Real-time PCR for simultaneous detection and genotyping of bovine viraldiarrhea virus. Journal of Virological Methods2003,114:21-27.
123. Letellier C., et al. Detection and genotyping of bovine diarrhea virus by reversetranscription-polymerase chain amplification of the5′untranslated region. Veterinary Microbiology1999，64：155-167.
124. Levine B., et al. Development by self-digestion: molecular mechanisms and biological functions ofautophagy. Developmental Cell2004,6:463-477.
125. Li D., et al. Hemoglobin subunit beta interacts with the capsid protein and antagonizes the growthof classical swine fever virus. Journal of Virology2013a,87:5707-5717.
126. Li D., et al. Poly （C）-binding protein1, a novel npro-interacting protein involved in classicalSwine Fever virus growth. Journal of Virology2013b,87:2072-2080.
127. Li J.K., et al. Autophagy is involved in the early step of Japanese encephalitis virus infection.Microbes and Infection2012,14:159-168.
128. Liang D., et al. The envelope glycoprotein E2is a determinant of cell culture tropism in ruminantpestiviruses. Journal of General Virology2003,84:1269-1274.
129. Liang X.H., et al. Protection against fatal Sindbis virus encephalitis by beclin, a novelBcl-2-interacting protein. Journal of Virology1998,72:8586-8596.
130. Lin W., et al. Hepatitis C virus core protein blocks interferon signaling by interaction with theSTAT1SH2domain. Journal of Virology2006,80:9226-9235.
131. Liu B., et al. Negative regulation of NF-κB signaling by PIAS1. Molecular and Cellular Biology2005,25:1113-1123.
132. Liu L., et al. Virus recovery and full-length sequence analysis of atypical bovine pestivirusTh/04_KhonKaen. Veterinary Microbiology2009a,138:62-68.
133. Liu L., et al. Maximum likelihood and Bayesian analyses of a combined nucleotide sequencedataset for genetic characterization of a novel pestivirus, SVA/cont-08. Arch Virol2009b,154:1111-1116.
134. Liu Q., et al. Autophagy sustains the replication of porcine reproductive and respiratory virus inhost cells. Virology2012,429:136-147.
135. M tzener P., et al. The viral RNase Erns prevents IFN type-I triggering by pestiviral single-anddouble-stranded RNAs. Virus Research2009,140:15-23.
136. Macdonald A., et al. The hepatitis C virus non-structural NS5A protein inhibits activating protein-1function by perturbing ras-ERK pathway signaling. The Journal of Biological Chemistry2003,278:17775-17784.
137. Mahony T.J., et al. Genetic analysis of bovine viral diarrhoea viruses from Australia. VeterinaryMicrobiology2005,106:1-6.
138. Maurer K., et al. CD46is a cellular receptor for bovine viral diarrhea virus. Journal of Virology2004,78:1792-1799.
139. Mayer D., et al. Attenuation of classical swine fever virus by deletion of the viral Nprogene.Vaccine2004,22:317-328.
140. McDermott C.M. Guidelines for the use and interpretation of assays for monitoring autophagy.Autophagy2012,8:445-544.
141. McFadden A., et al. The first case of a bull persistently infected with Border disease virus in NewZealand. New Zealand Veterinary Journal2012,60:290-296.
142. McLauchlan J. Properties of the hepatitis C virus core protein: a structural protein that modulatescellular processes. Journal of Viral Hepatitis2000,7:2-14.
143. Meyling A., et al. Epidemiology of bovine virus diarrhoea virus. Revue Scientifique etTechnique-Office International des épizooties1990,9:75-93.
144. Mishra N., et al. Evidence of a humoral immune response against the prokaryotic expressedN-terminal autoprotease （Npro） protein of bovine viral diarrhoea virus. Journal of Biosciences2010,35:79-86.
145. Mishra N., et al. Identification of bovine viral diarrhea virus type1in yaks （Bos poephagusgrunniens） in the Himalayan region. Research in Veterinary Science2008,84:507-510.
146. Miyasaka Y., et al. Hepatitis C virus nonstructural protein5A inhibits tumor necrosisfactor-alpha-mediated apoptosis in Huh7cells. The Journal of Infectious Diseases2003,188:1537-1544.
147. Moy R.H., et al. Antiviral Autophagy Restricts Rift Valley Fever Virus Infection and Is Conservedfrom Flies to Mammals. Immunity2014,40:51-65.
148. Murray C.L., et al. Bovine viral diarrhea virus core is an intrinsically disordered protein that bindsRNA. Journal of Virology2008,82:1294-1304.
149. Nagai M., et al. Identification of new genetic subtypes of bovine viral diarrhea virus genotype1isolated in Japan. Virus Genes2008,36:135-139.
150. Nitahara-Kasahara Y., et al. Cellular vimentin content regulates the protein level of hepatitis Cvirus core protein and the hepatitis C virus production in cultured cells. Virology2009,383:319-327.
151. O'Donnell V., et al. Foot-and-mouth disease virus utilizes an autophagic pathway during viralreplication. Virology2011,410:142-150.
152. Olafson P., et al. An apparently new transmissible disease of cattle. The Cornell Veterinarian1946,36:205.
153. Orvedahl A., et al. Autophagy protects against Sindbis virus infection of the central nervous system.Cell Host&Microbe2010,7:115-127.
154. Patterson R., et al. Yeast-surface expressed BVDV E2protein induces a Th1/Th2response in na veT cells. Developmental&Comparative Immunology2012,37:107-114.
155. Pavlovi D., et al. The hepatitis C virus p7protein forms an ion channel that is inhibited bylong-alkyl-chain iminosugar derivatives. Proceedings of the National Academy of Sciences2003,100:6104-6108.
156. Pei J., et al. Autophagy enhances the replication of classical swine fever virus in vitro. Autophagy2013,10:93-110.
157. Peletto S., et al. Detection and phylogenetic analysis of an atypical pestivirus, strain IZSPLV_To.Research in Veterinary Science2012,92:147-150.
158. Peterhans E., et al. BVDV and innate immunity. Biologicals: journal of the InternationalAssociation of Biological Standardization2003,31:107-112.
159. Pinchuk G.V., et al. Bovine viral diarrhea viruses differentially alter the expression of the proteinkinases and related proteins affecting the development of infection and anti-viral mechanisms inbovine monocytes. Biochimica et Biophysica Acta2008,1784:1234-1247.
160. Potgieter L. Bovine respiratory tract disease caused by bovine viral diarrhea virus. The Veterinaryclinics of North America. Food Animal Practice1997,13:471-481.
161. Potgieter L., et al. Comparison of the pneumopathogenicity of two strains of bovine viral diarrheavirus. American Journal of Veterinary Research1985,46:151.
162. Presi P., et al. Bovine viral diarrhea （BVD） eradication in Switzerland—experiences of the firsttwo years. Preventive Veterinary Medicine2011,99:112-121.
163. Pypers A., et al. Fatal congenital anaplasmosis associated with bovine viral diarrhoea virus（BVDV） infection in a crossbred calf. Journal of the South African Veterinary Association2011,82:179-182.
164. Rümenapf T., et al. N-terminal protease of pestiviruses: identification of putative catalytic residuesby site-directed mutagenesis. Journal of Virology1998,72:2544-2547.
165. Ray R.B., et al. Hepatitis C virus core protein: intriguing properties and functional relevance.FEMS Microbiology Letters2001,202:149-156.
166. Reyes G.R. The nonstructural NS5A protein of hepatitis C virus: an expanding, multifunctional rolein enhancing hepatitis C virus pathogenesis. Journal of Biomedical Science2002,9:187-197.
167. Richetta C., et al. Autophagy in antiviral innate immunity.2012.
168. Ridpath J.F. BVDV genotypes and biotypes: practical implications for diagnosis and control.Biologicals: Journal of the International Association of Biological Standardization2003,31:127-131.
169. Robesova B., et al. Genotyping of bovine viral diarrhoea virus isolates from the Czech Republic.Veterinarni Medicina2009,54:393-398.
170. Rytinki M.M., et al. PIAS proteins: pleiotropic interactors associated with SUMO. Cellular andMolecular Life Sciences2009,66:3029-3041.
171. Saliki J.T., et al. Laboratory diagnosis of bovine viral diarrhea virus infections. Veterinary Clinicsof North America: Food Animal Practice2004,20:69-83.
172. Schelp C., et al. BVD diagnosis: an overview. Berliner und Munchener tierarztliche Wochenschrift2003,116:227.
173. Schirrmeier H., et al. Genetic and antigenic characterization of an atypical pestivirus isolate, aputative member of a novel pestivirus species. The Journal of General Virology2004,85:3647-3652.
174. Schmid D., et al. Innate and adaptive immunity through autophagy. Immunity2007,27:11-21.
175. Schweizer M., et al.“Self” and “nonself” manipulation of interferon defense during persistentinfection: bovine viral diarrhea virus resists alpha/beta interferon without blocking antiviral activityagainst unrelated viruses replicating in its host cells. Journal of Virology2006,80:6926-6935.
176. Seago J., et al. The Npro product of classical swine fever virus and bovine viral diarrhea virus usesa conserved mechanism to target interferon regulatory factor-3. The Journal of General Virology2007,88:3002-3006.
177. Shahriar F.M., et al. Coinfection with bovine viral diarrhea virus and Mycoplasma bovis in feedlotcattle with chronic pneumonia. The Canadian Veterinary Journal2002,43:863.
178. Sharrocks A.D. PIAS proteins and transcriptional regulation—more than just SUMO E3ligases?Genes&development2006,20:754-758.
179. Shelly S., et al. Autophagy Is an Essential Component of Drosophila Immunity against VesicularStomatitis Virus. Immunity2009,30:588-598.
180. Shrivastava S., et al. Hepatitis C virus upregulates Beclin1for induction of autophagy and activatesmTOR signaling. Journal of Virology2012,86:8705-8712.
181. Shrivastava S., et al. Knockdown of autophagy enhances the innate immune response in hepatitis Cvirus–infected hepatocytes. Hepatology2011,53:406-414.
182. Shuai K. Regulation of cytokine signaling pathways by PIAS proteins. Cell Research2006,16:196-202.
183. Shuai K., et al. Regulation of gene-activation pathways by PIAS proteins in the immune system.Nature Reviews Immunology2005,5:593-605.
184. Smirnova N.P., et al. Acute non-cytopathic bovine viral diarrhea virus infection inducespronounced type I interferon response in pregnant cows and fetuses. Virus Res2008,132:49-58.
185. Srikumaran S., et al. The use of bovine MHC class I allele-specific peptide motifs and proteolyticcleavage specificities for the prediction of potential cytotoxic T lymphocyte epitopes of bovine viraldiarrhea virus. Virus Genes1997,14:111-121.
186. St hl K., et al. Natural infection of cattle with an atypicalHoBi'-like pestivirus–Implications forBVD control and for the safety of biological products. Veterinary Research2007,38:517-523.
187. Stalder H.P., et al. Genetic heterogeneity of pestiviruses of ruminants in Switzerland. PreventiveVeterinary Medicine2005,72:37-41; discussion215-219.
188. Stokka G.L., et al. Bovine virus diarrhea. Kansas State University Agricultural Experiment Stationand Cooperative Extension Service.2000
189. Strandberg L., et al. Factors influencing inclusion body formation in the production of a fusedprotein in Escherichia coli. Applied and Environmental Microbiology1991,57:1669-1674.
190. Sun Y., et al. Autophagy benefits the replication of Newcastle disease virus in chicken cells andtissues. Journal of Virology2014,88:525-537.
191. Suzuki K., et al. The pre-autophagosomal structure organized by concerted functions of APG genesis essential for autophagosome formation. The EMBO Journal2001,20:5971-5981.
192. Tahk S., et al. Control of specificity and magnitude of NF-κB and STAT1-mediated gene activationthrough PIASy and PIAS1cooperation. Proceedings of the National Academy of Sciences2007,104:11643-11648.
193. Tai D.I., et al. Activation of nuclear factor κB in hepatitis C virus infection: implications forpathogenesis and hepatocarcinogenesis. Hepatology2000,31:656-664.
194. Tajima M. The prevalent genotypes of bovine viral diarrhea virus in Japan, Germany and theUnited States of America. Japanese Journal of Veterinary Research2006,54:129-134.
195. Tajima M., et al. Prevalence of genotypes1and2of bovine viral diarrhea virus in Lower Saxony,Germany. Virus Research2001,76:31-42.
196. Takeda K., et al. Toll-like receptors in innate immunity. International Immunology2005,17:1-14.
197. Tanaka Y., et al. Selective binding of hepatitis C virus core protein to synthetic oligonucleotidescorresponding to the5′untranslated region of the viral genome. Virology2000,270:229-236.
198. Tao J., et al. Bovine viral diarrhea virus （BVDV） infections in pigs. Veterinary Microbiology2013,165:185-189.
199. Taylor L.F., et al. The prevalence of bovine viral diarrhea virus infection in a population of feedlotcalves in western Canada. Canadian Journal of Veterinary Research1995,59:87.
200. Taylor M.P., et al. Modification of cellular autophagy protein LC3by poliovirus. Journal ofVirology2007,81:12543-12553.
201. Tellinghuisen T.L., et al. Interaction between hepatitis C virus proteins and host cell factors.Current Opinion in Microbiology2002,5:419-427.
202. Toplak I., et al. Genetic typing of bovine viral diarrhoea virus: most Slovenian isolates are ofgenotypes1d and1f. Veterinary Microbiology2004,99:175-185.
203. Topliff C.L., et al. Prevalence of bovine viral diarrhea virus infections in alpacas in the UnitedStates. Journal of the American Veterinary Medical Association2009,234:519-529.
204. Underdahl N., et al. Cultivation in tissue-culture of cytopathogenic agent from bovine mucosaldisease. Proceedings of the Society for Experimental Biology and Medicine. Society forExperimental Biology and Medicine （New York, NY）1957,795-797.
205. Van Campen H., et al. Isolation of bovine viral diarrhea virus from a free-ranging mule deer inWyoming. Journal of Wildlife Diseases2001,37:306-311.
206. Vilcek S., et al. Genetic diversity of BVDV: consequences for classification and molecularepidemiology. Preventive Veterinary Medicine2005,72:31-35.
207. Vilcek S., et al. Genetic diversity of recent bovine viral diarrhoea viruses from the southeast ofAustria （Styria）. Veterinary Microbiology2003,91:285-291.
208. Vil ek., et al. Bovine viral diarrhoea virus genotype1can be separated into at least elevengenetic groups. Archives of Virology2001,146:99-115.
209. Warrilow D., et al. Properties of the bovine viral diarrhoea virus replicase in extracts of infectedMDBK cells. Archives of Virology2000,145:2163-2171.
210. Wong J., et al. Autophagosome supports coxsackievirus B3replication in host cells. Journal ofVirology2008,82:9143-9153.
211. Xia H., et al. Detection and identification of the atypical bovine pestiviruses in commercial foetalbovine serum batches. PloS One2011,6: e28553.
212. Xu X., et al. Sequencing and comparative analysis of a pig bovine viral diarrhea virus genome.Virus Research2006,122:164-170.
213. Xue F., et al. Genotyping of bovine viral diarrhea viruses from cattle in China between2005and
2008. Veterinary Microbiology2010,143:379-383.
214. Yang D.K., et al. Genetic typing of bovine viral diarrhea viruses （BVDV） circulating in Korea.Journal of Bacteriology and Virology2007,37:147-152.
215. Yao Z.Q., et al. Hepatitis C virus core protein inhibits human T lymphocyte responses by acomplement-dependent regulatory pathway. The Journal of Immunology2001,167:5264-5272.
216. Yilmaz H., et al. Genetic diversity and frequency of bovine viral diarrhea virus（BVDV） detectedin cattle in Turkey. Comparative Immunology, Microbiology and Infectious Diseases2012,35:411-416.
217. Yoneyama M., et al. RNA recognition and signal transduction by RIG‐I‐like receptors.Immunological Reviews2009,227:54-65.
218. Yoshida T., et al. Activation of STAT3by the hepatitis C virus core protein leads to cellulartransformation. The Journal of Experimental Medicine2002,196:641-653.
219. Yueh A., et al. Interaction of moloney murine leukemia virus capsid with Ubc9and PIASymediates SUMO-1addition required early in infection. Journal of Virology2006,80:342-352.
220. Zemke J., et al. Novel BVDV-2mutants as new candidates for modified-live vaccines. VeterinaryMicrobiology2010,142:69-80.
221. Zhang J.J., et al. Genetic diversity of bovine viral diarrhoea virus in Beijing region, China from2009to2010. African Journal of Microbiology Research2013,7:4934-4939.
222. Zhong F., et al. Genetic typing and epidemiologic observation of bovine viral diarrhea virus inWestern China. Virus Genes2011,42:204-207.
223. Zhou Z., et al. Autophagy is involved in influenza A virus replication. Autophagy2009,5:321-328.
224. Zhu L., et al. Identification of a Bovine viral diarrhea virus2isolated from cattle in China. ActaVirologica2009,53:131-134.
225. Zhu, N., et al. Hepatitis C virus core protein binds to the cytoplasmic domain of tumor necrosisfactor （TNF） receptor1and enhances TNF-induced apoptosis. Journal of Virology1998,72:3691-3697.
2.贺生录，等.牛病毒性腹泻/粘膜病流行情况调查[J].青海畜牧兽医杂志，1991，1：17.
3.韩志辉，等.牦牛病毒性腹泻/粘膜病和传染性鼻气管炎血清学调查[J].中国动物传染病学报，2010，18（6）：56-59.
4.李佑民，等.牛病毒性腹泻-粘膜病病毒（长春184）的分离与鉴定[J].中国人民解放军兽医大学学报，1983，3（2）：113-120.
5.任敏.基因2型牛病毒性腹泻病毒的分离、鉴定[硕士学位论文]乌鲁木齐：新疆农业大学，2007
6.任敏，等.基因2型牛病毒性腹泻病毒新疆及山东分离株的鉴定[J].中国动物传染病学报，2009，17（4）：20-24.
7.沈艳丽，等.青海省玉树地区牛病毒性腹泻-粘膜病血清学调查[J].中国动物检疫，2011，28（10）：52.
8.宋永峰，等.猪源牛病毒性腹泻病毒的流行初探[J].中国动物检疫，2008（7）：25-27.
9.王新平，等.从疑似猪瘟病料中检出牛病毒性腹泻病毒[J].中国兽医学报，1996b，16（4）：341-345.
10.王新平，等.牛病毒性腹泻病毒P125基因重要区的比较与分析[J].中国兽医学报，1996a，16（6）：546-553.
11. Agnello V., et al. Hepatitis C virus and other flaviviridae viruses enter cells via low densitylipoprotein receptor. Proceedings of the National Academy of Sciences1999,96:12766-12771.
12. Aguirre I., et al. Antigenic variability in bovine viral diarrhea virus （BVDV） isolates from alpaca（Vicugna pacos）, llama（Lama glama）and bovines in Chile. Veterinary Microbiology2014,168:324-330.
13. Akira S., et al. Pathogen recognition and innate immunity. Cell2006,124:783-801.
14. Archambault D., et al. Clinical response and immunomodulation following experimental challengeof calves with type2noncytopathogenic bovine viral diarrhea virus. Veterinary Research2000,31:215-227.
15. Arora T., et al. PIASx is a transcriptional co-repressor of signal transducer and activator oftranscription4. Journal of Biological Chemistry2003,278:21327-21330.
16. Atluru D., et al. Suppression of in vitro immunoglobulin biosynthesis in bovine spleen cells bybovine viral diarrhea virus. Clinical Immunology and Immunopathology1979,13:254-260.
17. Baigent S.J., et al. Differential activation of interferon regulatory factors-3and-7bynon-cytopathogenic and cytopathogenic bovine viral diarrhoea virus. Veterinary Immunology andImmunopathology2004,100:135-144.
18. Baker J.C. The clinical manifestations of bovine viral diarrhea infection. The Veterinary clinics ofNorth America. Food Animal Practice1995,11:425.
19. Bauhofer O., et al. Classical swine fever virus Npro interacts with interferon regulatory factor3andinduces its proteasomal degradation. Journal of Virology2007,81:3087-3096.
20. Becher P., et al. Genetic diversity of pestiviruses: identification of novel groups and implications forclassification. Virology1999,262:64-71.
21. Bhatia S., et al. Development and evaluation of a MAb based competitive-ELISA using helicasedomain of NS3protein for sero-diagnosis of bovine viral diarrhea in cattle and buffaloes. Researchin Veterinary Science2008,85:39-45.
22. Bhudevi B., et al. Fluorogenic RT–PCR assay（TaqMan） for detection and classification of bovineviral diarrhea virus. Veterinary Microbiology2001,83:1-10.
23. Bhudevi B., et al. Detection of bovine viral diarrhea virus in formalin fixed paraffin embeddedtissue sections by real time RT-PCR （Taqman）. Journal of virological methods2003,109:25-30.
24. Biuk-Rudan N., et al. Prevalence of antibodies to IBR and BVD viruses in dairy cows withreproductive disorders. Theriogenology1999,51:875-881.
25. Booth R.E., et al. A phylogenetic analysis of Bovine Viral Diarrhoea Virus （BVDV） isolates fromsix different regions of the UK and links to animal movement data. Veterinary Research2013,44:
43.
26. Branza-Nichita N., et al. Antiviral Effect ofN-Butyldeoxynojirimycin against Bovine Viral DiarrheaVirus Correlates with Misfolding of E2Envelope Proteins and Impairment of Their Association intoE1-E2Heterodimers. Journal of Virology2001,75:3527-3536.
27. Brodersen B., et al. Effect of concurrent experimentally induced bovine respiratory syncytial virusand bovine viral diarrhea virus infection on respiratory tract and enteric diseases in calves.American journal of Veterinary Research1998,59:1423-1430.
28. Brodersen B.W., et al. Alteration of leukocyte populations in calves concurrently infected withbovine respiratory syncytial virus and bovine viral diarrhea virus. Viral Immunology1999,12:323-334.
29. Brownlie J., et al. Maternal recognition of foetal infection with bovine virus diarrhoea virus（BVDV）—the bovine pestivirus. Clinical and Diagnostic Virology1998,10:141-150.
30. Buckingham E.M., et al. Autophagy and the effects of its inhibition on varicella-zoster virusglycoprotein biosynthesis and infectivity. Journal of Virology2014,88:890-902.
31. Byers S.R., et al. Disseminated bovine viral diarrhea virus in a persistently infected alpaca（Vicugna pacos） cria. Journal of Veterinary Diagnostic Investigation2009,21:145-148.
32. Carman S., et al. Bovine viral diarrhea virus in alpaca: abortion and persistent infection. Journal ofVeterinary Diagnostic Investigation2005,17:589-593.
33. Charleston B., et al. Masking of two in vitro immunological assays for Mycobacterium bovis（BCG） in calves acutely infected with non-qctopathic bovine viral diarrhoea virus. VeterinaryRecord2001,149:481-484.
34. Chase C.C. The impact of BVDV infection on adaptive immunity. Biologicals: Journal of theInternational Association of Biological Standardization2013,41:52-60.
35. Chase C.C., et al. The immune response to bovine viral diarrhea virus: a constantlychanging picture.Veterinary Clinics of North America: Food Animal Practice2004,20:95-114.
36. Chaumorcel M., et al. Human cytomegalovirus controls a new autophagy-dependent cellularantiviral defense mechanism. Autophagy2008,4:46-53.
37. Chen Q., et al. Induction of autophagy enhances porcine reproductive and respiratory syndromevirus replication. Virus Research2012,163:650-655.
38. Chung C.D., et al. Specific inhibition of Stat3signal transduction by PIAS3. Science1997,278:1803-1805.
39. Cleveland S.M., et al. Assessment of a bovine viral diarrhea virus antigen capture ELISA and amicrotiter virus isolation ELISA using pooled ear notch and serum samples. Journal of VeterinaryDiagnostic Investigation2006,18:395-398.
40. Collen T., et al. Analysis of the repertoire of cattle CD4（+） T cells reactive with bovine viraldiarrhoea virus. Veterinary Immunology and Immunopathology2002a,87:235-238.
41. Collins M.E., et al. Infectivity of pestivirus following persistence of acute infection. VeterinaryMicrobiology2009,138:289-296.
42. Cornish T.E., et al. Comparison of ear notch immunohistochemistry, ear notch antigen-captureELISA, and buffy coat virus isolation for detection of calves persistently infected with bovine viraldiarrhea virus. Journal of Veterinary Diagnostic Investigation2005,17:110-117.
43. Cortez A., et al. Genetic characterization of Brazilian bovine viral diarrhea virus isolates by partialnucleotide sequencing of the5'-UTR region. Pesquisa Veterinária Brasileira2006,26:211-216.
44. Cowley D.B., et al. Bovine viral diarrhoea virus seroprevalence and vaccination usage in dairy andbeef herds in the Republic of Ireland. Irish Veterinary Journal2012,65:1-9.
45. Decaro N., et al. Atypical pestivirus and severe respiratory disease in calves, Europe. EmergingInfectious Diseases2011,17:1549.
46. Deng Y., et al. High prevalence of bovine viral diarrhea virus1in Chinese swine herds. VeterinaryMicrobiology2012,159:490-493.
47. Driskell E.A., et al. A survey of bovine viral diarrhea virus testing in diagnostic laboratories in theUnited States from2004to2005. Journal of Veterinary Diagnostic Investigation2006,18:600-605.
48. Eiras C., et al. Bovine viral diarrhea virus Correlation between herd seroprevalence and bulk tankmilk antibody levels using4commercial immunoassays. Journal of Veterinary DiagnosticInvestigation2012,24:549-553.
49. Eisen-Vandervelde A.L., et al. Hepatitis C virus core selectively suppresses interleukin-12synthesisin human macrophages by interfering with AP-1activation. Journal of Biological Chemistry2004,279:43479-43486.
50. Elahi S.M., et al. Induction of humoral and cellular immune responses against the nucleocapsid ofbovine viral diarrhea virus by an adenovirus vector with an inducible promoter. Virology1999,261:1-7.
51. Ellis J., et al. Effect of maternal antibodies on induction and persistence of vaccine-induced immuneresponses against bovine viral diarrhea virus type II in young calves. Journal of The AmericanVeterinary Medical Association2001,219:351-356.
52. Endsley J.J., et al. Maternal antibody blocks humoral but not T cell responses to BVDV.Biologicals: journal of the International Association of Biological Standardization2003,31:123-125.
53. Falcone E., et al. Genetic heterogeneity of bovine viral diarrhoea virus in Italy. Veterinary ResearchCommunications,2003,27:485-494.
54. Fields S., et al. A novel genetic system to detect protein protein interactions.1989.
55. Fliss P.M., et al. Viral mediated redirection of NEMO/IKKγ to autophagosomes curtails theinflammatory cascade. PLoS Pathogens2012,8: e1002517.
56. Flores E.F., et al. Phylogenetic analysis of Brazilian bovine viral diarrhea virus type2（BVDV-2）isolates: evidence for a subgenotype within BVDV-2. Virus Research2002,87:51-60.
57. Foster A., et al. Bovine viral diarrhoea virus infection of alpacas （Vicugna pacos） in the UK.Veterinary Record2007,161:94-99.
58. Fredriksen B., et al. Level and duration of serum antibodies in cattle infected experimentally andnaturally with bovine virus diarrhoea virus. Veterinary Record1999,144:111-114.
59. Fulton R.W., et al. Bovine viral diarrhea virus （BVDV）1b: predominant BVDV subtype in calveswith respiratory disease. Canadian Journal of Veterinary Research2002,66:181.
60. Fulton R.W., et al. Prevalence of bovine viral diarrhea virus （BVDV） in persistently infectedcattle and BVDV subtypes in affected cattle in beef herds in south central United States. CanadianJournal of Veterinary Research2009,73:283.
61. Fux R., et al. Transient elimination of circulating bovine viral diarrhea virus by colostral antibodiesin persistently infected calves: a pitfall for BVDV-eradication programs? Veterinary Microbiology.2012,161:13-19.
62. Gamlen T., et al. Expression of the NS3protease of cytopathogenic bovine viral diarrhea virusresults in the induction of apoptosis but does not block activation of the beta interferon promoter.Journal of General Virology2010,91:133-144.
63. Gannagé M., et al. Matrix protein2of influenza A virus blocks autophagosome fusion withlysosomes. Cell Host&Microbe2009,6:367-380.
64. Gao J., et al. Seroprevalence of bovine viral diarrhea infection in Yaks （Bos grunniens） on theQinghai-Tibetan Plateau of China. Tropical Animal Health and Production2013a,45:791-793.
65. Gao S., et al. Serological and molecular evidence for natural infection of Bactrian camels withmultiple subgenotypes of bovine viral diarrhea virus in Western China. Veterinary Microbiology2013b,163:172-176.
66. Gao Y., et al. Isolation and identification of a bovine viral diarrhea virus from sika deer in china.Virology Journal2011,8:83.
67. Gil L.H., et al. The amino-terminal domain of bovine viral diarrhea virus Npro protein is necessaryfor alpha/beta interferon antagonism. Journal of Virology2006,80:900-911.
68. Gladue D., et al. Interaction between Core protein of classical swine fever virus with cellularIQGAP1protein appears essential for virulence in swine. Virology2011,412:68-74.
69. Gladue D.P., et al. Effects of the interactions of classical swine fever virus Core protein withproteins of the SUMOylation pathway on virulence in swine. Virology2010,407:129-136.
70. Glew E.J., et al. Antigen-presenting cells from calves persistently infected with bovine viraldiarrhoea virus, a member of the Flaviviridae, are not compromised in their ability to present viralantigen. Journal of General Virology2001,82:1677-1685.
71. Gong X., et al. Identification and characterization of a novel subgenotype of bovine viral diarrheavirus isolated from dairy cattle in Northwestern China. Virus Genes,2013,46:375-376
72. Goyal S.M., et al. Bovine viral diarrhea virus: diagnosis, management, and control.2008.
73. Grégoire I.P., et al. IRGM is a common target of RNA viruses that subvert the autophagy network.PLoS Pathogens2011,7: e1002422.
74. Grummer B., et al. Localization of viral proteins in cells infected with bovine viral diarrhoea virus.The Journal of General Virology2001,82:2597-2605.
75. Hansen T.H., et al. MHC class I antigen presentation: learning from viral evasion strategies. NatureReviews Immunology2009,9:503-513.
76. Hansen T.R., et al. Maternal and Fetal Response to Fetal Persistent Infection with Bovine ViralDiarrhea Virus*. American Journal of Reproductive Immunology2010,64:295-306.
77. Hara H., et al. Involvement of creatine kinase B in hepatitis C virus genome replication throughinteraction with the viral NS4A protein. Journal of Virology2009,83:5137-5147.
78. Hengel H., et al. Viruses know it all: new insights into IFN networks. Trends in Immunology2005,26:396-401.
79. Hiscott J., et al. Hostile takeovers: viral appropriation of the NF-kB pathway. Journal of ClinicalInvestigation2001,107:143-151.
80. Hiscott J., et al. MasterCARD: a priceless link to innate immunity. Trends in Molecular Medicine2006,12:53-56.
81. Horscroft N., et al. Establishment of a subgenomic replicon for bovine viral diarrhea virus in Huh-7cells and modulation of interferon-regulated factor3-mediated antiviral response. Journal ofVirology2005,79:2788-2796.
82. Houe H. Economic impact of BVDV infection in dairies. Biologicals: journal of the InternationalAssociation of Biological Standardization2003,31:137-143.
83. Houe H., et al. Test strategies in bovine viral diarrhea virus control and eradication campaigns inEurope. Journal of Veterinary Diagnostic Investigation2006,18:427-436.
84. Hulst M., et al. Passage of classical swine fever virus in cultured swine kidney cells selects virusvariants that bind to heparan sulfate due to a single amino acid change in envelope protein Erns.Journal of Virology,2000,74:9553-9561.
85. Hwang E.J., et al. SUMOylation of RORα potentiates transcriptional activation function.Biochemical and Biophysical Research Communications2009,378:513-517.
86. Iqbal M., et al. Interactions of bovine viral diarrhoea virus glycoprotein Erns with cell surfaceglycosaminoglycans. Journal of General Virology2000,81:451-459.
87. Itsui Y., et al. Antiviral effects of the interferon‐induced protein guanylate binding protein1and itsinteraction with the hepatitis C virus NS5B protein. Hepatology2009,50:1727-1737.
88. Jackova A., et al. The extended genetic diversity of BVDV-1: typing of BVDV isolates from France.Veterinary Research Communications2008,32:7-11.
89. Johns H.L., et al. The classical swine fever virus N-terminal protease Npro binds to cellular HAX-1.Journal of General Virology2010,91:2677-2686.
90. Johnson C.M., et al. The NS5A protein of bovine viral diarrhoea virus interacts with the alphasubunit of translation elongation factor-1. The Journal of General Virology2001,82:2935-2943.
91. Jones L.R., et al. Application of single-strand conformation polymorphism to the study of bovineviral diarrhea virus isolates. Journal of Veterinary Diagnostic Investigation: official publication ofthe American Association of Veterinary Laboratory Diagnosticians, Inc2001,13:50-56.
92. Jones L.R., et al. Genetic typing of bovine viral diarrhea virus isolates from Argentina. VeterinaryMicrobiology2001,81:367-375.
93. Jounai N., et al. The Atg5–Atg12conjugate associates with innate antiviral immune responses.Proceedings of the National Academy of Sciences2007,104:14050-14055.
94. Kabeya Y., et al. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosomemembranes after processing. The EMBO Journal2000,19:5720-5728.
95. Kadir Y., et al. Genetic heterogeneity of bovine viral diarrhoea virus （BVDV） isolates fromTurkey: identification of a new subgroup in BVDV-1. Veterinary Microbiology2008,130:258-267.
96. Kampa J., et al. Bovine herpesvirus type1（BHV-1） and bovine viral diarrhoea virus （BVDV）infections in dairy herds: self clearance and the detection of seroconversions against a new atypicalpestivirus. The Veterinary Journal2009,182:223-230.
97. Kato H., et al. Differential roles of MDA5and RIG-I helicases in the recognition of RNA viruses.Nature2006,441:101-105.
98. Kawai T., et al. Innate immune recognition of viral infection. Nature Immunology2006,7:131-137.
99. Kennedy J.A. Diagnostic efficacy of a reverse transcriptase–polymerase chain reaction assay toscreen cattle for persistent bovine viral diarrhea virus infection. Journal of the American VeterinaryMedical Association2006,229:1472-1474.
100. Khan F., et al. Evaluation of the effects of long-term storage of bovine ear notch samples on theability of2diagnostic assays to identify calves persistently infected with bovine viral diarrhoeavirus. Journal of the South African Veterinary Association2011,82:18-23.
101. Kihara A., et al. Beclin–phosphatidylinositol3-kinase complex functions at the trans-Golginetwork. EMBO reports2001,2:330-335.
102. Kim S.G., et al. A novel simple one-step single-tube RT-duplex PCR method with an internalcontrol for detection of bovine viral diarrhoea virus in bulk milk, blood, and follicular fluid samples.Biologicals: Journal of the International Association of Biological Standardization2003,31:103-106.
103. Kirkegaard K. Subversion of the cellular autophagy pathway by viruses. Infection and Immunity2009, Springer:323-333.
104. Klionsky D.J. Autophagy: from phenomenology to molecular understanding in less than a decade.Nature Reviews Molecular Cell Biology2007,8:931-937.
105. Klionsky D.J., et al. A unified nomenclature for yeast autophagy-related genes. DevelopmentalCell2003,5:539-545.
106. KLIU INSKAS R., et al. Detection of bovine viral diarrhoea virus in saliva samples. Bull Vet InstPulawy2008,52:31-37.
107. Knight Z., et al. Chemically targeting the PI3K family. Biochemical Society Transactions2007,35:245-249.
108. Kroemer G., et al. Autophagy and the integrated stress response. Molecular Cell2010,40:280-293.
109. Kubota T., et al. PIASy inhibits virus-induced and interferon-stimulated transcription throughdistinct mechanisms. Journal of Biological Chemistry2011,286:8165-8175.
110. Kuhne S., et al. Detection of bovine viral diarrhoea virus infected cattle–testing tissue samplesderived from ear tagging using an Erns capture ELISA. Journal of Veterinary Medicine, Series B2005,52:272-277.
111. Kuta A., et al. Predominance of bovine viral diarrhea virus1b and1d subtypes during eight yearsof survey in Poland. Veterinary Microbiology2013,166:639-644.
112. La Rocca S.A., et al. Loss of interferon regulatory factor3in cells infected with classical swinefever virus involves the N-terminal protease, Npro. Journal of Virology2005,79:7239-7247.
113. Lai M., et al. Hepatitis C virus core protein: possible roles in viral pathogenesis. The Hepatitis CViruses.2000, Springer:117-134.
114. Lambot M., et al. Characterization of the immune response of cattle against non-cytopathic andcytopathic biotypes of bovine viral diarrhoea virus. Journal of General Virology1997,78:1041-1047.
115. Lambot M., et al. Evidence for biotype-specific effects of bovine viral diarrhoea virus on biologicalresponses in acutely infected calves. Journal of General Virology1998,79:27-30.
116. Lan S.Y., et al. Direct interaction between alpha-actinin and hepatitis C virus NS5B. Febs Lett2003,554:289-294.
117. Lanyon S.R., et al. Bovine viral diarrhoea: Pathogenesis and diagnosis. Veterinary Journal.2013.
118. Lee H.K., et al. Autophagy-dependent viral recognition by plasmacytoid dendritic cells. Science2007,315:1398-1401.
119. Lee S.R., et al. Bovine viral diarrhea viruses modulate toll-like receptors, cytokines andco-stimulatory molecules genes expression in bovine peripheral blood monocytes. ComparativeImmunology, Microbiology and Infectious Diseases2008a,31:403-418.
120. Lee Y.R., et al. Autophagic machinery activated by dengue virus enhances virus replication.Virology2008b,374:240-248.
121. Leib D.A., et al. Interaction of ICP34.5with Beclin1modulates herpes simplex virus type1pathogenesis through control of CD4+T-cell responses. Journal of Virology2009,83:12164-12171.
122. Letellier C., et al. Real-time PCR for simultaneous detection and genotyping of bovine viraldiarrhea virus. Journal of Virological Methods2003,114:21-27.
123. Letellier C., et al. Detection and genotyping of bovine diarrhea virus by reversetranscription-polymerase chain amplification of the5′untranslated region. Veterinary Microbiology1999，64：155-167.
124. Levine B., et al. Development by self-digestion: molecular mechanisms and biological functions ofautophagy. Developmental Cell2004,6:463-477.
125. Li D., et al. Hemoglobin subunit beta interacts with the capsid protein and antagonizes the growthof classical swine fever virus. Journal of Virology2013a,87:5707-5717.
126. Li D., et al. Poly （C）-binding protein1, a novel npro-interacting protein involved in classicalSwine Fever virus growth. Journal of Virology2013b,87:2072-2080.
127. Li J.K., et al. Autophagy is involved in the early step of Japanese encephalitis virus infection.Microbes and Infection2012,14:159-168.
128. Liang D., et al. The envelope glycoprotein E2is a determinant of cell culture tropism in ruminantpestiviruses. Journal of General Virology2003,84:1269-1274.
129. Liang X.H., et al. Protection against fatal Sindbis virus encephalitis by beclin, a novelBcl-2-interacting protein. Journal of Virology1998,72:8586-8596.
130. Lin W., et al. Hepatitis C virus core protein blocks interferon signaling by interaction with theSTAT1SH2domain. Journal of Virology2006,80:9226-9235.
131. Liu B., et al. Negative regulation of NF-κB signaling by PIAS1. Molecular and Cellular Biology2005,25:1113-1123.
132. Liu L., et al. Virus recovery and full-length sequence analysis of atypical bovine pestivirusTh/04_KhonKaen. Veterinary Microbiology2009a,138:62-68.
133. Liu L., et al. Maximum likelihood and Bayesian analyses of a combined nucleotide sequencedataset for genetic characterization of a novel pestivirus, SVA/cont-08. Arch Virol2009b,154:1111-1116.
134. Liu Q., et al. Autophagy sustains the replication of porcine reproductive and respiratory virus inhost cells. Virology2012,429:136-147.
135. M tzener P., et al. The viral RNase Erns prevents IFN type-I triggering by pestiviral single-anddouble-stranded RNAs. Virus Research2009,140:15-23.
136. Macdonald A., et al. The hepatitis C virus non-structural NS5A protein inhibits activating protein-1function by perturbing ras-ERK pathway signaling. The Journal of Biological Chemistry2003,278:17775-17784.
137. Mahony T.J., et al. Genetic analysis of bovine viral diarrhoea viruses from Australia. VeterinaryMicrobiology2005,106:1-6.
138. Maurer K., et al. CD46is a cellular receptor for bovine viral diarrhea virus. Journal of Virology2004,78:1792-1799.
139. Mayer D., et al. Attenuation of classical swine fever virus by deletion of the viral Nprogene.Vaccine2004,22:317-328.
140. McDermott C.M. Guidelines for the use and interpretation of assays for monitoring autophagy.Autophagy2012,8:445-544.
141. McFadden A., et al. The first case of a bull persistently infected with Border disease virus in NewZealand. New Zealand Veterinary Journal2012,60:290-296.
142. McLauchlan J. Properties of the hepatitis C virus core protein: a structural protein that modulatescellular processes. Journal of Viral Hepatitis2000,7:2-14.
143. Meyling A., et al. Epidemiology of bovine virus diarrhoea virus. Revue Scientifique etTechnique-Office International des épizooties1990,9:75-93.
144. Mishra N., et al. Evidence of a humoral immune response against the prokaryotic expressedN-terminal autoprotease （Npro） protein of bovine viral diarrhoea virus. Journal of Biosciences2010,35:79-86.
145. Mishra N., et al. Identification of bovine viral diarrhea virus type1in yaks （Bos poephagusgrunniens） in the Himalayan region. Research in Veterinary Science2008,84:507-510.
146. Miyasaka Y., et al. Hepatitis C virus nonstructural protein5A inhibits tumor necrosisfactor-alpha-mediated apoptosis in Huh7cells. The Journal of Infectious Diseases2003,188:1537-1544.
147. Moy R.H., et al. Antiviral Autophagy Restricts Rift Valley Fever Virus Infection and Is Conservedfrom Flies to Mammals. Immunity2014,40:51-65.
148. Murray C.L., et al. Bovine viral diarrhea virus core is an intrinsically disordered protein that bindsRNA. Journal of Virology2008,82:1294-1304.
149. Nagai M., et al. Identification of new genetic subtypes of bovine viral diarrhea virus genotype1isolated in Japan. Virus Genes2008,36:135-139.
150. Nitahara-Kasahara Y., et al. Cellular vimentin content regulates the protein level of hepatitis Cvirus core protein and the hepatitis C virus production in cultured cells. Virology2009,383:319-327.
151. O'Donnell V., et al. Foot-and-mouth disease virus utilizes an autophagic pathway during viralreplication. Virology2011,410:142-150.
152. Olafson P., et al. An apparently new transmissible disease of cattle. The Cornell Veterinarian1946,36:205.
153. Orvedahl A., et al. Autophagy protects against Sindbis virus infection of the central nervous system.Cell Host&Microbe2010,7:115-127.
154. Patterson R., et al. Yeast-surface expressed BVDV E2protein induces a Th1/Th2response in na veT cells. Developmental&Comparative Immunology2012,37:107-114.
155. Pavlovi D., et al. The hepatitis C virus p7protein forms an ion channel that is inhibited bylong-alkyl-chain iminosugar derivatives. Proceedings of the National Academy of Sciences2003,100:6104-6108.
156. Pei J., et al. Autophagy enhances the replication of classical swine fever virus in vitro. Autophagy2013,10:93-110.
157. Peletto S., et al. Detection and phylogenetic analysis of an atypical pestivirus, strain IZSPLV_To.Research in Veterinary Science2012,92:147-150.
158. Peterhans E., et al. BVDV and innate immunity. Biologicals: journal of the InternationalAssociation of Biological Standardization2003,31:107-112.
159. Pinchuk G.V., et al. Bovine viral diarrhea viruses differentially alter the expression of the proteinkinases and related proteins affecting the development of infection and anti-viral mechanisms inbovine monocytes. Biochimica et Biophysica Acta2008,1784:1234-1247.
160. Potgieter L. Bovine respiratory tract disease caused by bovine viral diarrhea virus. The Veterinaryclinics of North America. Food Animal Practice1997,13:471-481.
161. Potgieter L., et al. Comparison of the pneumopathogenicity of two strains of bovine viral diarrheavirus. American Journal of Veterinary Research1985,46:151.
162. Presi P., et al. Bovine viral diarrhea （BVD） eradication in Switzerland—experiences of the firsttwo years. Preventive Veterinary Medicine2011,99:112-121.
163. Pypers A., et al. Fatal congenital anaplasmosis associated with bovine viral diarrhoea virus（BVDV） infection in a crossbred calf. Journal of the South African Veterinary Association2011,82:179-182.
164. Rümenapf T., et al. N-terminal protease of pestiviruses: identification of putative catalytic residuesby site-directed mutagenesis. Journal of Virology1998,72:2544-2547.
165. Ray R.B., et al. Hepatitis C virus core protein: intriguing properties and functional relevance.FEMS Microbiology Letters2001,202:149-156.
166. Reyes G.R. The nonstructural NS5A protein of hepatitis C virus: an expanding, multifunctional rolein enhancing hepatitis C virus pathogenesis. Journal of Biomedical Science2002,9:187-197.
167. Richetta C., et al. Autophagy in antiviral innate immunity.2012.
168. Ridpath J.F. BVDV genotypes and biotypes: practical implications for diagnosis and control.Biologicals: Journal of the International Association of Biological Standardization2003,31:127-131.
169. Robesova B., et al. Genotyping of bovine viral diarrhoea virus isolates from the Czech Republic.Veterinarni Medicina2009,54:393-398.
170. Rytinki M.M., et al. PIAS proteins: pleiotropic interactors associated with SUMO. Cellular andMolecular Life Sciences2009,66:3029-3041.
171. Saliki J.T., et al. Laboratory diagnosis of bovine viral diarrhea virus infections. Veterinary Clinicsof North America: Food Animal Practice2004,20:69-83.
172. Schelp C., et al. BVD diagnosis: an overview. Berliner und Munchener tierarztliche Wochenschrift2003,116:227.
173. Schirrmeier H., et al. Genetic and antigenic characterization of an atypical pestivirus isolate, aputative member of a novel pestivirus species. The Journal of General Virology2004,85:3647-3652.
174. Schmid D., et al. Innate and adaptive immunity through autophagy. Immunity2007,27:11-21.
175. Schweizer M., et al.“Self” and “nonself” manipulation of interferon defense during persistentinfection: bovine viral diarrhea virus resists alpha/beta interferon without blocking antiviral activityagainst unrelated viruses replicating in its host cells. Journal of Virology2006,80:6926-6935.
176. Seago J., et al. The Npro product of classical swine fever virus and bovine viral diarrhea virus usesa conserved mechanism to target interferon regulatory factor-3. The Journal of General Virology2007,88:3002-3006.
177. Shahriar F.M., et al. Coinfection with bovine viral diarrhea virus and Mycoplasma bovis in feedlotcattle with chronic pneumonia. The Canadian Veterinary Journal2002,43:863.
178. Sharrocks A.D. PIAS proteins and transcriptional regulation—more than just SUMO E3ligases?Genes&development2006,20:754-758.
179. Shelly S., et al. Autophagy Is an Essential Component of Drosophila Immunity against VesicularStomatitis Virus. Immunity2009,30:588-598.
180. Shrivastava S., et al. Hepatitis C virus upregulates Beclin1for induction of autophagy and activatesmTOR signaling. Journal of Virology2012,86:8705-8712.
181. Shrivastava S., et al. Knockdown of autophagy enhances the innate immune response in hepatitis Cvirus–infected hepatocytes. Hepatology2011,53:406-414.
182. Shuai K. Regulation of cytokine signaling pathways by PIAS proteins. Cell Research2006,16:196-202.
183. Shuai K., et al. Regulation of gene-activation pathways by PIAS proteins in the immune system.Nature Reviews Immunology2005,5:593-605.
184. Smirnova N.P., et al. Acute non-cytopathic bovine viral diarrhea virus infection inducespronounced type I interferon response in pregnant cows and fetuses. Virus Res2008,132:49-58.
185. Srikumaran S., et al. The use of bovine MHC class I allele-specific peptide motifs and proteolyticcleavage specificities for the prediction of potential cytotoxic T lymphocyte epitopes of bovine viraldiarrhea virus. Virus Genes1997,14:111-121.
186. St hl K., et al. Natural infection of cattle with an atypicalHoBi'-like pestivirus–Implications forBVD control and for the safety of biological products. Veterinary Research2007,38:517-523.
187. Stalder H.P., et al. Genetic heterogeneity of pestiviruses of ruminants in Switzerland. PreventiveVeterinary Medicine2005,72:37-41; discussion215-219.
188. Stokka G.L., et al. Bovine virus diarrhea. Kansas State University Agricultural Experiment Stationand Cooperative Extension Service.2000
189. Strandberg L., et al. Factors influencing inclusion body formation in the production of a fusedprotein in Escherichia coli. Applied and Environmental Microbiology1991,57:1669-1674.
190. Sun Y., et al. Autophagy benefits the replication of Newcastle disease virus in chicken cells andtissues. Journal of Virology2014,88:525-537.
191. Suzuki K., et al. The pre-autophagosomal structure organized by concerted functions of APG genesis essential for autophagosome formation. The EMBO Journal2001,20:5971-5981.
192. Tahk S., et al. Control of specificity and magnitude of NF-κB and STAT1-mediated gene activationthrough PIASy and PIAS1cooperation. Proceedings of the National Academy of Sciences2007,104:11643-11648.
193. Tai D.I., et al. Activation of nuclear factor κB in hepatitis C virus infection: implications forpathogenesis and hepatocarcinogenesis. Hepatology2000,31:656-664.
194. Tajima M. The prevalent genotypes of bovine viral diarrhea virus in Japan, Germany and theUnited States of America. Japanese Journal of Veterinary Research2006,54:129-134.
195. Tajima M., et al. Prevalence of genotypes1and2of bovine viral diarrhea virus in Lower Saxony,Germany. Virus Research2001,76:31-42.
196. Takeda K., et al. Toll-like receptors in innate immunity. International Immunology2005,17:1-14.
197. Tanaka Y., et al. Selective binding of hepatitis C virus core protein to synthetic oligonucleotidescorresponding to the5′untranslated region of the viral genome. Virology2000,270:229-236.
198. Tao J., et al. Bovine viral diarrhea virus （BVDV） infections in pigs. Veterinary Microbiology2013,165:185-189.
199. Taylor L.F., et al. The prevalence of bovine viral diarrhea virus infection in a population of feedlotcalves in western Canada. Canadian Journal of Veterinary Research1995,59:87.
200. Taylor M.P., et al. Modification of cellular autophagy protein LC3by poliovirus. Journal ofVirology2007,81:12543-12553.
201. Tellinghuisen T.L., et al. Interaction between hepatitis C virus proteins and host cell factors.Current Opinion in Microbiology2002,5:419-427.
202. Toplak I., et al. Genetic typing of bovine viral diarrhoea virus: most Slovenian isolates are ofgenotypes1d and1f. Veterinary Microbiology2004,99:175-185.
203. Topliff C.L., et al. Prevalence of bovine viral diarrhea virus infections in alpacas in the UnitedStates. Journal of the American Veterinary Medical Association2009,234:519-529.
204. Underdahl N., et al. Cultivation in tissue-culture of cytopathogenic agent from bovine mucosaldisease. Proceedings of the Society for Experimental Biology and Medicine. Society forExperimental Biology and Medicine （New York, NY）1957,795-797.
205. Van Campen H., et al. Isolation of bovine viral diarrhea virus from a free-ranging mule deer inWyoming. Journal of Wildlife Diseases2001,37:306-311.
206. Vilcek S., et al. Genetic diversity of BVDV: consequences for classification and molecularepidemiology. Preventive Veterinary Medicine2005,72:31-35.
207. Vilcek S., et al. Genetic diversity of recent bovine viral diarrhoea viruses from the southeast ofAustria （Styria）. Veterinary Microbiology2003,91:285-291.
208. Vil ek., et al. Bovine viral diarrhoea virus genotype1can be separated into at least elevengenetic groups. Archives of Virology2001,146:99-115.
209. Warrilow D., et al. Properties of the bovine viral diarrhoea virus replicase in extracts of infectedMDBK cells. Archives of Virology2000,145:2163-2171.
210. Wong J., et al. Autophagosome supports coxsackievirus B3replication in host cells. Journal ofVirology2008,82:9143-9153.
211. Xia H., et al. Detection and identification of the atypical bovine pestiviruses in commercial foetalbovine serum batches. PloS One2011,6: e28553.
212. Xu X., et al. Sequencing and comparative analysis of a pig bovine viral diarrhea virus genome.Virus Research2006,122:164-170.
213. Xue F., et al. Genotyping of bovine viral diarrhea viruses from cattle in China between2005and
2008. Veterinary Microbiology2010,143:379-383.
214. Yang D.K., et al. Genetic typing of bovine viral diarrhea viruses （BVDV） circulating in Korea.Journal of Bacteriology and Virology2007,37:147-152.
215. Yao Z.Q., et al. Hepatitis C virus core protein inhibits human T lymphocyte responses by acomplement-dependent regulatory pathway. The Journal of Immunology2001,167:5264-5272.
216. Yilmaz H., et al. Genetic diversity and frequency of bovine viral diarrhea virus（BVDV） detectedin cattle in Turkey. Comparative Immunology, Microbiology and Infectious Diseases2012,35:411-416.
217. Yoneyama M., et al. RNA recognition and signal transduction by RIG‐I‐like receptors.Immunological Reviews2009,227:54-65.
218. Yoshida T., et al. Activation of STAT3by the hepatitis C virus core protein leads to cellulartransformation. The Journal of Experimental Medicine2002,196:641-653.
219. Yueh A., et al. Interaction of moloney murine leukemia virus capsid with Ubc9and PIASymediates SUMO-1addition required early in infection. Journal of Virology2006,80:342-352.
220. Zemke J., et al. Novel BVDV-2mutants as new candidates for modified-live vaccines. VeterinaryMicrobiology2010,142:69-80.
221. Zhang J.J., et al. Genetic diversity of bovine viral diarrhoea virus in Beijing region, China from2009to2010. African Journal of Microbiology Research2013,7:4934-4939.
222. Zhong F., et al. Genetic typing and epidemiologic observation of bovine viral diarrhea virus inWestern China. Virus Genes2011,42:204-207.
223. Zhou Z., et al. Autophagy is involved in influenza A virus replication. Autophagy2009,5:321-328.
224. Zhu L., et al. Identification of a Bovine viral diarrhea virus2isolated from cattle in China. ActaVirologica2009,53:131-134.
225. Zhu, N., et al. Hepatitis C virus core protein binds to the cytoplasmic domain of tumor necrosisfactor （TNF） receptor1and enhances TNF-induced apoptosis. Journal of Virology1998,72:3691-3697.