全球口蹄疫防控技术及病原特性研究概观

doi:10.3864/j.issn.0578-1752.2015.17.020

摘要/Abstract

摘要： 口蹄疫是危害猪牛羊等主要家畜畜种的疫病，可造成巨大的经济损失，引发严重的负面社会影响，被中国政府列在一类动物疫病的首位。中国猪、牛、羊养殖量最大、邻国众多，防控口蹄疫不仅对本国农牧业发展起关键作用，而且对全球口蹄疫防控有重要意义。目前，除一些发达国家消灭了口蹄疫并保持着无疫状态外，口蹄疫仍在众多发展中国家流行或散发。中国周边口蹄疫疫情不断，对中国造成高压威胁，近年流行的O/ME-SA/PanAsia、O/SEA/Mya-98和A/ASIA/Sea-97病毒均是传入的。从周边流行的病毒、流行的频率和循环的区域位置判断，O/PanAsia-2、A/Iran-05、Asia1/Sindh-08和O/Ind-2001病毒未来威胁依然较大。几十年来，中国不断完善各级兽医服务体系，充分发挥国家口蹄疫参考实验室科研带动、技术指导、疫情监控的职能，采取疫苗强制免疫为主的防控政策，卓有成效。依照世界动物卫生组织（OIE）推荐的口蹄疫渐进控制路线图（PCP-FMD），中国目前处于阶段3。推进口蹄疫防控效果进入更高阶段，关键在诊断检测技术和疫苗。自主研发的液相阻断ELISA、非结构蛋白3ABC抗体检测ELISA、多重RT-PCR等已达世界先进水平，有力支撑了中国口蹄疫诊断检测工作，并在朝鲜、越南等国应用。新一代测序、胶体金和纳米示踪材料标记免疫层析和生物反应效应分子检测等更精准便捷的新技术，未来也有望在口蹄疫诊断中实现应用。全病毒灭活疫苗免疫效力最优，是目前应用的主要疫苗，但存在干扰鉴别诊断等缺陷。随着免疫学理论和基因工程技术的进步，发展和应用标记疫苗、活载体疫苗、表位蛋白疫苗和病毒颗粒样疫苗等新型疫苗是未来的趋势。近十余年来，反向遗传操作凭借其定向改造基因组等强大技术优势，不仅促进了标记疫苗等新型基因工程疫苗的研发，而且推动了口蹄疫病毒宿主嗜性、复制机制、受体利用和先天性免疫应答等方面的基础研究，取得的研究成果必将有力推动防控应用型研究的进步。

关键词: 口蹄疫, 流行现状, 防控新技术, 病原特性

Abstract: Foot-and-mouth disease (FMD) is a highly infectious disease of head livestock, e.g. pigs, cattle and sheep, and may cause enormous economic losses and serious negative social problems. It is ranked first in the A list of infectious diseases of animals in China. As a largest country for pigs, cattle, sheep and goats farming and a country with lots of neighboring countries, FMD prevention and control is not only crucial for the development of animal husbandry in China, but also of significance for the global FMD prevention and control. Nowadays, except some developed countries where FMD was eradicated and the FMD-free status has been maintained, prevalence and outbreaks of FMD happen in most of developing countries. China suffers a serious threat from the continued outbreak of FMD in neighboring countries. O/ME-SA/PanAsia, O/SEA/Mya-98 and A/ASIA/Sea-97, FMDV lineages epidemic in China in recent years, were came from neighboring countries. Based on the analyses of the epidemic lineages in surrounding countries, frequency of outbreak and locations of circulation, O/PanAsia-2, A/Iran-05, Asia1/Sindh-08 and O/Ind-2001 are the epidemic lineages threatening China in the future. For decades, veterinary service systems at all levels have been constantly improved in China, the functions (e.g. scientific research, technical guidance, epidemic monitoring) of National FMD Reference Laboratory have been given full exerting and compulsory immunization and prevention-oriented policy have been proven to be highly effective. Based on the progressive control pathway for FMD (PCP-FMD) recommended by OIE (Office International des Epizootics), the effect of prevention and control in China is in the third stage of PCP-FMD. To promote the effect of FMD prevention and control into a higher level, the keys are the diagnostic testing technology and vaccines. The liquid-phase blocking enzyme linked immunosorbent assay (ELISA), non-structural protein 3ABC antibody detecting ELISA, multiplex reverse transcription-polymerase chain reaction (RT-PCR) and other independent research and development products have reached the world advanced level, strongly supporting the FMD diagnostic testing in China and also applied in North Korea, Vietnam and other countries. New generation of sequencing technology, colloidal gold and nanometre tracer tag immune chromatography, biological response effect of molecular detection and other more punctual and more convenient technologies are expected to achieve application in FMD diagnosis in the future. As the most widely used vaccine, FMD inactivated vaccine has the optimal immunization effect, apart from interference to differentiate between FMDV infected and vaccinated animals. Along with the progress of the immunology theory and genetic engineering technology, marker vaccine, live carrier vaccine, protein epitope vaccine, virus-like particles vaccine and other new type vaccines will be developed and applied in the future. In the last ten years, with its powerful technical advantages, such as directional changes in FMDV genome, reverse genetics promoted not only the research and development of marker vaccine and other new type of genetic engineering vaccines, but also FMDV basic research, such as host tropism, replication mechanism, receptor usage and innate immune response, and the basic research will vigorously promote the applied research of FMD prevention and control.

Key words: foot-and-mouth disease, epidemic status, new technologies for disease prevention and control, virus characteristics

刘在新. 全球口蹄疫防控技术及病原特性研究概观[J]. 中国农业科学, 2015, 48(17): 3547-3564.

LIU Zai-xin. Progress and Prospect of the Technologies to Control Foot-and- Mouth Disease and Its Pathogen Characteristics Worldwide[J]. Scientia Agricultura Sinica, 2015, 48(17): 3547-3564.

0
/ / 推荐

导出引用管理器 EndNote|Reference Manager|ProCite|BibTeX|RefWorks

链接本文: https://www.chinaagrisci.com/CN/10.3864/j.issn.0578-1752.2015.17.020

https://www.chinaagrisci.com/CN/Y2015/V48/I17/3547

参考文献

[1] 谢庆阁. 口蹄疫. 北京：中国农业出版社, 2004: 1-15.

Xie Q G. Foot-and-Mouth Disease. Beijing: China Agriculture Press, 2004:1-15. (in Chinese)

[2] WRLFMD: The foot-and-mouth disease home page. http://www.wrlfmd.org

[3] OIE: World animal health information system. http://www.oie.int/wahis

[4] Lu Z J, Cao Y M, Bao H F, Qi S Y, Guo J H, Shang Y J, Jiang T, Ma J W, Liu Z X, Yin H. Techniques development in China for foot-and-mouth disease diagnosis. Transboundary and Emerging Disease,2008, 55: 196-199.

[5] Fu Y F, Cao Y M, Sun P, Bao H F, Bai X W, Li P H, Li D, Lu Z J, Liu Z X. Development of a dot immunoblot method for differentiation of animals infected with foot-and-mouth disease virus vaccinated animals using non-structural preteins expressed prokaryotically. Journal of Virological Methods, 2011, 171: 234-240.

[6] Fu Y F, Lu Z J, Li P H, Cao Y M, Sun P, Tian M N, Wang N, Bao H F, Bai X W, Li D, Chen Y L, Liu Z X. Development of a blocking ELISA based on a monoclonal antibody against a predominant epitope in non-Structural protein 3B2 of foot-and-mouth disease virus for differentiating infected from vaccinated animals. PLoS One, 2014, 9(11): e111737.

[7] Lauring A S, Andino R. Quasispecies theory and the behavior of RNA viruses. PLoS Pathogens, 2010, 6(7): e1001005.

[8] Wright C F, Morelli M J, Thébaud G, Knowles N J, Herzyk P, Paton D J, Haydon D T, King D P. Beyond the consensus: dissecting within-host viral population diversity of foot -and-mouth disease virus by using next generation genome sequencing. Journal of Virology, 2011, 85(5): 2266-2275.

[9] Morelli M J, Wright C F, Knowles N J, Juleff N, Paton D J, King D P, Haydon D T. Evolution of foot-and-mouth disease virus intra-sample sequence diversity during serial transmission in bovine hosts. Veterinary Research, 2013, 44: 12.

[10] Logan G, Freimanis G L, King D J, Valdazo-González B, Bachanek- Bankowska K, Sanderson N D, Knowles N J, King D P, Cottam E M. A universal protocol to generate consensus level genome sequences for foot-and-mouth disease virus and other positive-sense polyadenylated RNA viruses using the Illumina MiSeq. BMC Genomics, 2014, 15: 828.

[11] Van Borm S l, Belák S, Freimanis G. Veterinary Infection Biology: Molecular Diagnostics and High-Throughput Strategies. Methods in Molecular Biology, 2015, 1247: 415-436.

[12] Reid S M, Ferris N P, Brüning A, Hutchings G H, Kowalska Z, Akerblom L. Development of a rapid chromatographic strip test for the pen-side detection of foot and mouth disease virus antigen. Journal of Virological Methods, 2001, 96(2): 189-202.

[13] Sugimura T, Suzuki T, Chatchawanchonteera A, Sinuwonkwar P, Tsuda T, Murakami Y. Application of latex beads agglutination test for the detection of the antibody against virus-infection-associated (VIA) antigen of Foot and Mouth Disease (FMD) virus. Journal of Veterinary Medical Science, 2000, 62 (7): 805-807.

[14] 蒋韬, 梁仲, 陈涓, 何继军, 吕律, 马维民, 刘在新, 刘湘涛. 口蹄疫病毒O、A、AsiaⅠ型定型诊断胶体金免疫层析方法的建立. 中国农业科学, 2008,41(11): 3801-3808.

Jiang T, Liang Z, Chen J, He J J, Lü L, Ma W M, Liu Z X, Liu X T. Development of a rapid gold immunochromatographic strip test for the diagnosis of foot-and-mouth disease virus O, A and Asia I type. Scientia Agricultura Sinica, 2008, 41(11): 3801-3808. (in Chinese)

[15] Wu L, Jiang T, Lu Z J, Yang Y M, Sun P, Liang Z, Li D, Fu Y F, Cao Y M, Liu X T, Liu Z X. Development and validation of a prokaryotically expressed foot-and-mouth disease virus nonstructural protein 2C’3AB-based immunochromatographic strip to differentiate between infected and vaccinated animals. Virology Journal, 2011, 8: 186.

[16] 任志奇, 吴英松, 刘天才. 新型免疫层析技术的研究进展. 广东医学, 2013, 34(2): 312-314.

Ren Z Q, Wu Y S, Liu T C. Progress of new immunochromatographic technologies. Guangdong Medical Journal, 2013, 34(2): 312-314. (in Chinese)

[17] Guo H C, Sun S Q. Lanthanide-doped upconverting phosphors for bioassay and therapy. Nanoscale, 2012, 4: 6692-6706.

[18] Parida S, Anderson J, Cox S J, Barnett P V, Paton D J. Secretory IgA as an indicator of oro-pharyngeal foot-and-mouth disease virus replication and as a tool for post vaccination surveillance. Vaccine, 2006, 24(8): 1107-1116.

[19] Dong Y Y, Xu Y, Liu Z X, Fu Y F, Ohashi T, Tanaka Y, Mawatari K, Kitamori T. Rapid screening swine foot-and-mouth disease virus using micro-ELISA system. Lab on a Chip, 2011, 11(13): 2153-2155.

[20] McFadden P. Tech. Sight. Biosensors. Broadband biodetection: Holmes on a chip. Science, 2002, 297(5589): 2075-2076.

[21] Rider T H, Petrovick M S, Nargi F E, Harper J D, Schwoebei E D, Mathews R H, Blanchard D J, Bortolin L T, Young A M, Chen J, Hollis. A B cell-based sensor for rapid identification of pathogens. Science, 2003, 301(5630): 213-215.

[22] Li P H, Bai X W, Sun P, Li D, Lu Z J, Cao Y M, Fu Y F, Bao H F, Chen Y L, Xie B X, Liu Z X. Evaluation of a genetically modified foot-and-mouth disease virus vaccine candidate generated by reverse genetics. BMC Veterinary Research, 2012, 8: 57.

[23] Fowler V L, Knowles N J, Paton D J, Barnett P V. Marker vaccine potential of a foot-and-mouth disease virus with a partial VP1 G-H loop deletion. Vaccine, 2010, 28: 3428-3434.

[24] Grubman M J, Baxt B. Foot-and-mouth disease. Clinical Microbiology Reviews, 2004, 17(2): 465-493.

[25] Uddowla S, Hollister J, Pacheco J M, Rodriguez L L, Rieder E. A safe foot-and-mouth disease vaccine platform with two negative markers for differentiating infected from vaccinated animals. Journal of Virology, 2012, 86: 11675-11685.

[26] Martin W B, Edwards L T. A field trial in South Africa of an attenuated vaccine against foot-and-mouth disease. Research in Veterinary Science, 1965, 6: 196-201.

[27] Li P H, Lu Z J, Bai X W, Li D, Sun P, Bao H F, Fu Y F, Cao Y M, Chen Y L, Xie B X, Liu Z X. Evaluation of a 3A-truncated foot-and-mouth disease virus in pigs for its potential as a marker vaccine. Veterinary Research, 2014, 45: 51.

[28] Berinstein A, Tami C, Taboga O, Smitsaart E, Carrillo E. Protective immunity against foot-and-mouth disease virus induced by a recombinant vaccinia virus. Vaccine, 2000, 18: 2231-2238.

[29] Moraes M P, Mayr G A, Mason P W, Grubman M J. Early protection against homologous challenge after a single dose of replication- defective human adenovirus type 5 expressing capsid proteins of foot-and-mouth disease virus(FMDV) strain A24. Vaccine, 2002, 20(11-12): 1631-1639.

[30] Kitson J D A, Burke K L, Pullen L A, Belsham G J, Almond J W. Chimeric polioviruses that include sequences derived from two independent antigenic sites of foot-and-mouth diseases virus (FMDV) induce neutralizing antibodies against FMDV in guinea pigs. Journal of Virology, 1991, 65(6): 3068-3075.

[31] 童武, 徐彦召, 周艳君, 姜一峰, 张善瑞, 王亚欣, 朱建平, 虞凌雪, 孙晶, 陈焕春, 童光志. 表达O型口蹄疫病毒保护性抗原表位重组PRRSV的构建及其鉴定. 生物工程学报, 2012, 28(12): 1431-1440.

Tong W, Xu Y Z, Zhou Y J, Jiang Y F, Zhang S R, Wang Y X, Zhu J P, Yu L X, Sun J, Chen H C, Tong G Z. Construction and identification of a recombinant PRRSV expressing protective antigens of type O foot-and-mouth disease virus. Sheng Wu Gong Cheng Xue Bao, 2012, 28(12): 1431-1440. (in Chinese)

[32] Huang L, Zhang F, Tang Q, Wei Y, Wu H, Guo L, Fu Y, Liu C. A recombinant porcine circovirus type 2 expressing the VP1 epitope of the type O foot-and-mouth disease virus is infectious and induce both PCV2 and VP1 epitope antibodies. Applied Microbiology and Biotechnology, 2014, 98(22): 9339-9350

[33] Abram C C, King A M Q, Belsham G J. Assembly of foot-and-mouth disease virus empty capsid synthesized by a vaccinia virus expression system. Journal of General Virology, 1995, 76: 3089-3098.

[34] Pacheco J M, Brum M C, Moraes M P, Golde W T, Grubman M J. Rapid protection of cattle from direct challenge with foot-and-mouth disease virus (FMDV) by a single inoculation with an adenovirus- vectored FMDV subunit vaccine. Virology, 2005, 337(2): 205-209.

[35] Brake D A, McIlhaney M, Miller T, Christianson K, Keene A, Lohnas G, Purcell C, Neilan J, Schutta C, Barrera J, Burrage T, Brough DE, Butman B T. Human adenovirus-vectored foot-and-mouth disease vaccines: establishment of a vaccine product profile through in vitro testing. Developments in Biologicals, 2012, 134: 123-133.

[36] Lu Z J, Bao H F, Cao Y M, Sun P, Guo J H, Li P H, Bai X W, Chen Y L, Xie B X, Li D, Liu Z X, Xie Q G. Protection of guinea pigs and swine by a recombinant adenovirus expressing O serotype of foot-and-mouth disease virus whole capsid and 3C protease. Vaccine, 2008, 26S: G48-G53.

[37] Kim S M, Kim S K, Park J H, Lee K N, Ko Y J, Lee H S, Seo M G, Shin Y K, Kim B. A recombinant adenovirus bicistronically expressing porcine interferon-α and interferon-γ enhances antiviral effects against foot-and-mouth disease virus. Antiviral Research, 2014, 104:52-58.

[38] Zhang Z W, Pan L, Ding Y Z, Zhou P, Lv J L, Chen H T, Fang Y Z, Liu X S, Chang H Y, Zhang J, Shao J J, Lin T, Zhao F R, Zhang Y G, Wang Y L. Efficacy of synthetic peptide candidate vaccines against serotype-A foot-and-mouth disease virus in cattle. Applied Microbiology and Biotechnology, 2014, 09 November, published online.

[39] Volpina O M, Surovoy A Y, Zhmak M N, Kuprianova M A, Koroev D O, Chepurkin A V, Toloknov A S, Ivanov V T. A peptide construct containing B-cell and T-cell epitopes from the foot-and-mouth disease viral VP1 protein induces efficient antiviral protection. Vaccine, 1999, 17(6): 577-584.

[40] Cubillos C, de la Torre B G, Jakab A, Clementi G, Borrás E, Bárcena J, Andreu D, Sobrino F, Bianco E. Enhanced mucosal immunoglobulin A response and solid protection against foot-and-mouth disease virus challenge induced by a novel dendrimeric peptide. Journal of Virology, 2008, 82(14): 7223-7230.

[41] Shao J J, Wong C K, Lin T, Lee S K, Cong G Z, Sin F W, Du J Z, Gao S D, Liu X T, Cai X P, Chang H Y, Liu J X. Promising Multiple-epitope recombinant vaccine against foot-and-mouth disease virus type O in swine. Clinical and Vaccine Immunology, 2011, 18(1): 143-149.

[42] Cao Y M, Lu Z J, Li Y L, Sun P, Li D, Li P H, Bai X W, Fu Y F, Bao H F, Zhou C X, Xie B X, Chen Y L, Liu Z X. Poly (I: C) combined with multi-epitope protein vaccine completely protects against virulent foot-and-mouth disease virus challenge in pigs. Antiviral Research, 2013, 97: 145-153.

[43] Cao Y M, Lu Z J, Li D, Fan P J, Sun P, Bao H F, Fu Y F, Li P H, Bai X W, Chen Y L, Xie B X, Liu Z X. Evaluation of cross-protection against three topotypes of serotype O foot-and-mouth disease in pigs vaccinated with multi-epitope protein vaccine incorporated with poly(I:C). Veterinary Microbiology, 2014, 168: 294-301.

[44] Chackerian B. Virus-like particles: flexible platforms for vaccine development. Expert Review of Vaccines, 2007, 6(3): 381-390.

[45] Ludwig C, Wagner R. Virus-like particles-universal molecular tool boxes. Current Opinion in Biotechnology, 2007, 18(6): 537-545.

[46] Gamvrellis A, Leong D, Hanley J C, Xiang S D, Mottram P, Piebanski M. Vaccines that facilitate antigen entry into dendritic cells. Immunology and Cell Biology, 2004, 82(5): 506-516.

[47] Dong H, Guo H C, Sun S Q. Virus-like particles in picornavirus vaccine development. Applied of Microbiology and Biotechnology, 2014, 98: 4321-4329.

[48] Kleid D G, Yansura D, Small B, Dowbenko D, Moore D M, Grubman M J, McKercher P D, Morgan D O, Robertson B H, Bachrach H L. Cloned viral protein vaccine for foot-and-mouth disease: responses in cattle and swine. Science, 1981, 214(4525):1125-1129.

[49] Abrams C C, King A M, Belsham G J. Assembly of foot-and-mouth disease virus empty capsids synthesized by a vaccinia virus expression system. Journal of General Virology, 1995, 76(12): 3089-3098.

[50] Lee C D, Yan Y P, Liang S M, Wang T F. Production of FMDV virus-like particles by a SUMO fusion protein approach in Escherichia coli. Journal of Biomedical Science, 2009, 16: 69.

[51] Li Z Y, Yi Y Z, Yin X P, Zhang Z F, Liu J X. Expression of foot-and-mouth disease virus capsid proteins in silkworm-baculovirus expression system and its utilization as a subunit vaccine. PLoS One, 2008, 3(5): e2273.

[52] Cao Y M, Sun P, Fu Y F, Bai X W, Tian F P, Liu X T, Lu Z J, Liu Z X. Formation of virus-like particles from O-type foot-and-mouth disease virus in insect cells using codon-optimized synthetic genes. Biotechnology Letters, 2010, 32(9): 1223-1229.

[53] Guo H C, Sun S Q, Jin Y, Yang S L, Wei Y Q, Sun D H, Yin S H, Ma J W, Liu Z X, Guo J H, Luo J X, Yin H, Liu X T, Liu D X. Foot-and-mouth disease virus-like particles produced by a SUMO fusion protein system in Escherichia coli induce potent protective immune responses in guinea pigs, swine and cattle. Veterinary Research, 2013, 44: 48.

[54] Zibert A, Maass K, Strebel K, Falk M M, Beck E. Infectious foot-and-mouth disease virus derived from a cloned full-length cDNA. Journal of Virology, 1990, 64(6): 2467-2473.

[55] Rieder E, Bunch T, Brown F, Mason P W. Genetically engineered foot-and-mouth disease viruses with poly(C) tracts of two nucleotides are virulent in mice. Journal of Virology, 1993, 67(9): 5139-5145.

[56] Baranowski E, Molina N, Nunez J I, Sobrino F, Sáiz M. Recovery of infectious foot-and-mouth disease virus from sucking mice after direct inoculation with in vitro-transcribed RNA. Journal of Virology, 2003, 77(20): 11290-11295.

[57] Liu G, Liu Z, Xie Q, Chen Y L, Bao H F, Chang H Y, Liu X T. Generation of an infectious cDNA clone of an FMDV strain isolated from swine. Virus Research, 2004, 104: 157-164.

[58] Bai X, Bao H, Li P, Wei W, Zhang M, Sun P, Cao Y M, Lu Z J, Fu Y F, Xie B X, Chen Y L, Liu Z X. Effect of two amino acid substitutions in the capsid proteins on the interaction of two cell-adapted PanAsia-1 strains of foot-and-mouth disease virus serotype O with heparan sulfate receptor. Virology Journal, 2014, 11: 132.

[59] Li P H, Lu Z J, Bao H F, Li D, King D P, Sun P, Bai X W, Cao Y M, Gubbins S, Chen Y L, Xie B X, Guo J H, Yin H, Liu Z X. In-vitro and in-vivo phenotype of type Asia 1 foot-and-mouth disease viruses utilizing two non-RGD receptor recognition sites. BMC Microbiology, 2011, 11: 154.

[60] Dunn C S, Donaldson A I. Natural adaptation to pigs of a Taiwanese isolate of foot-and-mouth disease virus. Veterinary Record, 1997, 141: 174-175.

[61] Beard C W, Mason P W. Genetic determinants of altered virulence of Taiwanese foot-and-mouth disease virus. Journal of Virology, 2000, 74(2): 987-991.

[62] Pacheco J M, Henry T M, O’Donnell V K, Gregory J B, Mason P W. Role of nonstructural proteins 3A and 3B in host range and pathogenicity of foot-and-mouth disease virus. Journal of Virology, 2003, 77(24): 13017-13027.

[63] Pacheco J M, Gladue D P, Holinka L G, Arzt J, Bishop E, Smoliga G, Pauszek S J, Bracht A J, O’Donnell V, Fernandez-Sainz I, Fletcher P, Piccone M E, Rodriguez L L, Borca M V. A partial deletion in non-structural protein 3A can attenuate foot-and-mouth disease virus in cattle. Virology, 2013, 446: 260-267.

[64] Li P H, Bai X W, Sun P, Li D, Lu Z J, Cao Y M, Fu Y F, Bao H F, Chen Y L, Xie B X, Liu Z X. Evaluation of a genetically modified foot-and-mouth disease virus vaccine candidate generated by reverse genetics. BMC Veterinary Research, 2012, 8: 57.
[65] Valdazo-Gonzalez B, Timina A, Scherbakov A, Abdul-Hamid N F, Knowles N J, King D P. Multiple introductions of serotype O foot-and-mouth disease viruses into East Asia in 2010-2011. Veterinary Research, 2013, 44: 76.

[66] Ma X Q, Li P H, Bai X W, Sun P, Bao H F, Lu Z J, Cao Y M, Li D, Chen Y L, Qiao Z L, Liu Z X. Sequences outside that of residues 93-102 of 3A protein can contribute to the ability of foot-and-mouth disease virus (FMDV) to replicate in bovine-derived cells. Virus Research, 2014, 191: 161-171.

[67] Gonzalez-Magaldi M, Postigo R, Beatriz G, et al. Mutations that hamper dimerization of foot-and-mouth disease virus 3A protein are detrimental for infectivity. Journal of Virology, 2012, 86(20): 11013-11023.

[68] Gladue D P, O’Donnell V, Baker-Bransetter R, Pacheco J M, Holinka L G, Arzt J, Pauszek S, Fernandez-Sainz I, Flerher P, Brocchi E, Lu Z, Rodriguez L L, Borca M V. Interaction of foot-and-mouth disease virus non-structural protein 3A with host protein DCTN3 is important for viral virulence in cattle. Journal of Virology, 2013, 88(5): 2737-2747.

[69] Ruiz-Saenz J, Goez Y, Tabares W, Lopez-Herrera A. Cellular receptors for foot-and-mouth disease virus. Intervirology, 2009, 52(4): 201-212.

[70] Jackson T, Ellard F A, Ghazaleh R A, Brookes S M, Blakemore W E, Corteyn A H, Stuart D I, Newman J W I, King A M Q. Efficient infection of cells in culture by type O foot-and-mouth disease virus requires binding to cell surface heparin sulfate. Journal of Viroplogy, 1996, 70(8): 5282-5287.

[71] Zhao Q, Pacheco J, Mason P. Evalution of genetically engineered derivatives of a Chinese strain of foot-and-mouth disease virus reveals a novel cell-binding site which functions in cell culture and in animals. Journal of Virology, 2003, 77(5): 3269-3280.

[72] Zeng J, Wang H, Xie X, Li Chen, Zhou G H, Yang D C, Yu L. Ribavirin-restricted variants of foot-and-mouth disease virus: the effect of restriced quasispecies diversity on viral virulence. Journal of Virology, 2014, 88(8): 4008-4020.

[73] Du Y J, Bi J S, Liu J Y, Liu X, Wu X J, Jiang P, Yoo D W, Zhang Y G, Wu J Q, Wan R Z, Zhao X M, Guo L H, Sun W B, Cong X Y, Chen L, Wang J B. 3C^pro of foot-and-mouth disease virus antagonizes the interferon signaling pathway by blocking STAT1/STAT2 nuclear translocation. Journal of Virology, 2014, 88(9): 4908-4920.