非洲猪瘟病毒的分子病原学及致病机理研究进展

doi:10.16431/j.cnki.1671-7236.2017.07.033

摘要/Abstract

摘要：

非洲猪瘟（African swine fever，ASF）是由非洲猪瘟病毒（African swine fever virus，ASFV）引起的一种烈性传染病，具有急性、高热、高病死率等特征，主要暴发于非洲、东欧国家、俄罗斯及高加索地区。目前，该病缺乏有效的疫苗和治疗方法，给病情爆发地区的养猪业造成严重的影响。ASFV的主要靶细胞是网状内皮细胞和单核-巨噬细胞，造成细胞凋亡，影响宿主的免疫系统，进而表现出相应的疫病特征。ASFV具有基因组较大、基因型较多且易变异等特征。文章主要从分子病原学和致病机理方面对ASFV的研究情况进行综述，为ASF的防控提供理论依据。

关键词: 非洲猪瘟病毒; 分子病原学; 宿主; 致病机理

Abstract:

African swine fever (ASF) is a devastating disease caused by African swine fever virus (ASFV), characterized by acute feature, high fever, high mortality and other characteristics. ASF mainly outbreaks in African, Eastern Europe countries, Russia and Caucasus region. At present, there are no vaccine available and effective control strategies against ASFV spread, therefore, ASF has a serious impact on the pig industry in the affected countries. The major target cells of the virus are swine reticuloendothelial cells and monocyte-macrophage cells. ASFV can result in apoptosis and affect the host's immune system, and then show the characteristics of the corresponding disease. ASFV has the characteristics of large genome, more genotype and more variability. In this paper, the molecular etiology and pathogenesis of ASFV are reviewed, so as to provide theoretical basis for prevention and control of ASF.

Key words: African swine fever virus (ASFV); molecular etiology; host; pathogenesis

中图分类号:

S852.65

欧云文, 阎传忠, 张杰, 马炳, 代军飞, 张永光, 贾宁. 非洲猪瘟病毒的分子病原学及致病机理研究进展[J]. 《中国畜牧兽医》, 2017, 44(7): 2139-2146.

OU Yun-wen, YAN Chuan-zhong, ZHANG Jie, MA Bing, DAI Jun-fei, ZHANG Yong-guang, JIA Ning. Research Progress on Molecular Etiology and Pathogenesis for African Swine Fever Virus[J]. , 2017, 44(7): 2139-2146.

参考文献

[1] Penrith M L. African swine fever[J]. Onderstepoort Journal of Veterinary Research, 2009, 76(1):91-95.
[2] Costard S, Mur L, Lubroth J, et al. Epidemiology of frican swine fever virus[J]. Virus Research, 2013, 173(1):191-197.
[3] Sánchez-Vizcaíno J M, Mur L, Martínez-López B. African swine fever:An epidemiological update[J]. Transboundary and Emerging diseases, 2012, 59(1):27-35.
[4] Oganesyan A S, Petrova O N, Korennoy F I, et al. African swine fever in the Russian Federation:Spatio-temporal analysis and epidemiological overview[J]. Virus Research, 2013, 173(1):204-211.
[5] Sánchez-Vizcaíno J M, Mur L, Martínez-López B. African swine fever (ASF):Five years around Europe[J]. Veterinary Microbiology, 2013, 165(1):45-50.
[6] Chapman D A G, Tcherepanov V, Upton C, et al. Comparison of the genome sequences of non-pathogenic and pathogenic African swine fever virus isolates[J]. Journal of General Virology, 2008, 89(2):397-408.
[7] de Villiers E P, Gallardo C, Arias M, et al. Phylogenomic analysis of 11 complete African swine fever virus genome sequences[J]. Virology, 2010, 400(1):128-136.
[8] González A, Talavera A, Almendral J M, et al. Hairpin loop structure of African swine fever virus DNA[J]. Nucleic Acids Research, 1986, 14(17):6835-6844.
[9] Malogolovkin A, Burmakina G, Titov I, et al. Comparative analysis of African swine fever virus genotypes and serogroups[J]. Emerg Infect Dis, 2015, 21(2):312-315.
[10] Misinzo G, Magambo J, Masambu J, et al. Genetic characterization of African swine fever viruses from a 2008 outbreak in Tanzania[J]. Transboundary and Emerging Diseases, 2011, 58(1):86-92.
[11] Uttenthal ?, Braae U C, Ngowi H A, et al. ASFV in Tanzania:Asymptomatic pigs harbor virus of molecular similarity to Georgia 2007[J]. Veterinary Microbiology, 2013, 165(1):173-176.
[12] Atuhaire D K, Afayoa M, Ochwo S, et al. Molecular characterization and phylogenetic study of African swine fever virus isolates from recent outbreaks in Uganda (2010-2013)[J]. Virology Journal, 2013, 10(1):1-8.
[13] Luka P D, Achenbach J E, Mwiine F N, et al. Genetic characterization of circulating African swine fever viruses in Nigeria (2007-2015)[J]. Transboundary and Emerging Diseases, 2016,Epub ahead of print.
[14] Achenbach J E, Gallardo C, Nieto-Pelegrín E, et al. Identification of a new genotype of African swine fever virus in domestic pigs from Ethiopia[J]. Transboundary and Emerging Diseases, 2016,Epub ahead of print.
[15] Gallardo C, Mwaengo D M, Macharia J M, et al. Enhanced discrimination of African swine fever virus isolates through nucleotide sequencing of the p54, p72, and pB602L (CVR) genes[J]. Virus Genes, 2009, 38(1):85-95.
[16] Sanna G, Dei Giudici S, Bacciu D, et al. Improved strategy for molecular characterization of African swine fever viruses from Sardinia, based on analysis of p30, CD2V and I73R/I329L variable regions[J]. Transboundary and Emerging Diseases, 2016,Epub ahead of print.
[17] Carmina G, Jovita F P, Virginia P, et al. Genetic variation among African swine fever genotype Ⅱviruses, eastern and central Europe[J]. Emerging Infectious Diseases, 2014, 20(9):1544-1547.
[18] 李洪利, 曹金山, 王君玮,等. 非洲猪瘟病毒实时荧光定量PCR检测方法的建立及应用[J]. 中国畜牧兽医, 2012, 39(6):37-40.
[19] 李洪利, 王君玮, 张维,等. 非洲猪瘟病毒VP73蛋白主要抗原表位区的原核表达及多克隆抗体的制备[J]. 中国畜牧兽医, 2012, 39(10):7-10.
[20] 柏丽华, 侯绍华, 贾红,等. 非洲猪瘟P72基因在Bac to Bac系统中的表达及抗原性鉴定[J]. 中国畜牧兽医, 2012, 39(3):19-23.
[21] Zhou J, Gao Z, Sun D, et al. A comparative analysis on the synonymous codon usage pattern in viral functional genes and their translational initiation region of ASFV[J]. Virus Genes, 2013, 46(2):271-279.
[22] Mettenleiter T C, Sobrino F. Animal Viruses:Molecular Biology[M]. Norfolk:Caister Academic Press, 2008.
[23] Dixon L K, Chapman D A G, Netherton C L, et al. African swine fever virus replication and genomics[J]. Virus Research, 2013, 173(1):3-14.
[24] Suárez C, Salas M L, Rodríguez J M. African swine fever virus polyprotein pp62 is essential for viral core development[J]. Journal of Virology, 2010, 84(1):176-187.
[25] Andrés G, Alejo A, Salas J, et al. African swine fever virus polyproteins pp220 and pp62 assemble into the core shell[J]. Journal of Virology, 2002, 76(24):12473-12482.
[26] Malogolovkin A, Burmakina G, Tulman E R, et al. African swine fever virus CD2v and C-type lectin gene loci mediate serological specificity[J]. Journal of General Virology, 2015, 96(4):866-873.
[27] Pérez-Núñez D, García-Urdiales E, Martínez-Bonet M, et al. CD2v interacts with adaptor protein AP-1 during African swine fever infection[J]. PLoS One, 2015, 10(4):e0123714
[28] Borca M V, O'Donnell V, Holinka L G, et al. The Ep152R ORF of African swine fever virus strain Georgia encodes for an essential gene that interacts with host protein BAG6[J]. Virus Research, 2016, 223:181-189.
[29] Karalova E M, Sargsyan K V, Hampikian G K, et al. Phenotypic and cytologic studies of lymphoid cells and monocytes in primary culture of porcine bone marrow during infection of African swine fever virus[J]. In Vitro Cellular & Developmental Biology-Animal, 2011, 47(3):200-204.
[30] Karalyan Z, Zakaryan H, Arzumanyan H, et al. Pathology of porcine peripheral white blood cells during infection with African swine fever virus[J]. BMC Veterinary Research, 2012, 8:18.
[31] Blome S, Gabriel C, Beer M. Pathogenesis of African swine fever in domestic pigs and European wild boar[J]. Virus Research, 2013, 173(1):122-130.
[32] Howey E B, O'Donnell V, de Carvalho Ferreira H C, et al. Pathogenesis of highly virulent African swine fever virus in domestic pigs exposed via intraoropharyngeal, intranasopharyngeal, and intramuscular inoculation, and by direct contact with infected pigs[J]. Virus Research, 2013, 178(2):328-339.
[33] Galindo-Cardiel I, Ballester M, Solanes D, et al. Standardization of pathological investigations in the framework of experimental ASFV infections[J]. Virus Research, 2013, 173(1):180-190.
[34] de Carvalho Ferreira H C, Weesendorp E, Elbers A R W, et al. African swine fever virus excretion patterns in persistently infected animals:A quantitative approach[J]. Veterinary Microbiology, 2012, 160(3):327-340.
[35] Sánchez-Cordón P J, Chapman D, Jabbar T, et al. Different routes and doses influence protection in pigs immunised with the naturally attenuated African swine fever virus isolate OURT88/3[J]. Antiviral Research, 2016, 138:1-8.
[36] Post J, Weesendorp E, Montoya M, et al. Influence of age and dose of African swine fever virus infections on clinical outcome and blood parameters in pigs[J]. Viral Immunology, 2016, 30(1):58-69.
[37] Gogin A, Gerasimov V, Malogolovkin A, et al. African swine fever in the North Caucasus region and the Russian Federation in years 2007-2012[J]. Virus Research, 2013, 173(1):198-203.
[38] de Carvalho Ferreira H C, Weesendorp E, Quak S, et al. Quantification of airborne African swine fever virus after experimental infection[J]. Veterinary Microbiology, 2013, 165(3):243-251.
[39] Fraczyk M, Wo?niakowski G, Kowalczyk A, et al. Evolution of African swine fever virus genes related to evasion of host immune response[J]. Veterinary Microbiology, 2016, 193:133-144.
[40] Carlson J, O'Donnell V, Alfano M, et al. Association of the host immune response with protection using a live attenuated African swine fever virus model[J]. Viruses, 2016, 8(10):E291.
[41] Carrasco L, Nunez A, Salguero F J, et al. African swine fever:Expression of interleukin-1 alpha and tumour necrosis factor-alpha by pulmonary intravascular macrophages[J]. Journal of Comparative Pathology, 2002, 126(2):194-201.
[42] Luka P D, Erume J, Yakubu B, et al. Molecular detection of Torque teno sus virus and coinfection with African swine fever virus in blood samples of pigs from some slaughterhouses in Nigeria[J]. Advances in Virology, 2016, 2016(6):1-6.
[43] Pietschmann J, Mur L, Blome S, et al. African swine fever virus transmission cycles in Central Europe:Evaluation of wild boar-soft tick contacts through detection of antibodies against Ornithodoros erraticus saliva antigen[J]. Bmc Veterinary Research, 2016, 12(1):1-5.
[44] Burrage T G. African swine fever virus infection in Ornithodoros ticks[J]. Virus Research, 2013, 173(1):131-139.
[45] Bernard J, Hutet E, Paboeuf F, et al. Effect of O. porcinus tick salivary gland extract on the African swine fever virus infection in domestic pig[J]. PLoS One, 2016, 11(2):e0147869.
[46] Vallée I, Tait S W G, Powell P P. African swine fever virus infection of porcine aortic endothelial cells leads to inhibition of inflammatory responses, activation of the thrombotic state, and apoptosis[J]. Journal of Virology, 2001, 75(21):10372-10382.
[47] Munoz-Moreno R, Galindo I, Cuesta-Geijo M Á, et al. Host cell targets for African swine fever virus[J]. Virus Research, 2015, 209:118-127.
[48] Cuesta-Geijo M Á, Chiappi M, Galindo I, et al. Cholesterol flux is required for endosomal progression of African swine fever virions during the initial establishment of infection[J]. Journal of Virology, 2016, 90(3):1534-1543.
[49] Franzoni G, Graham S P, Giudici S D, et al. Characterization of the interaction of African swine fever virus with monocytes and derived macrophage subsets[J]. Veterinary Microbiology, 2016,198(1):88-98.
[50] Lithgow P, Takamatsu H, Werling D, et al. Correlation of cell surface marker expression with African swine fever virus infection[J]. Veterinary Microbiology, 2014, 168(2):413-419.
[51] Popescu L, Gaudreault N N, Whitworth K M, et al. Genetically edited pigs lacking CD163 show no resistance following infection with the African swine fever virus isolate, Georgia 2007/1[J]. Virology, 2017, 501:102-106.
[52] Neilan J G, Zsak L, Lu Z, et al. Neutralizing antibodies to African swine fever virus proteins p30, p54, and p72 are not sufficient for antibody-mediated protection[J]. Virology, 2004, 319(2):337-342.
[53] Sánchez E G, Quintas A, Pérez-Núñez D, et al. African swine fever virus uses macropinocytosis to enter host cells[J]. PLoS Pathogens, 2012, 8(6):356-363.
[54] Galindo I, Cuesta-Geijo M Á, Hlavova K, et al. African swine fever virus infects macrophages, the natural host cells, via clathrin-and cholesterol-dependent endocytosis[J]. Virus Research, 2015, 200:45-55.
[55] Bruno H, Milagros G, Salas M L, et al. African swine fever virus undergoes outer envelope disruption, capsid disassembly and inner envelope fusion before core release from multivesicular endosomes[J]. PLoS Pathogens, 2016, 12(4):e1005595.
[56] Andrés G. African swine fever virus gets undressed:New insights on the entry pathway[J]. J Virol, 2017,91(4):e01906-16.
[57] Rodríguez J M, Salas M L. African swine fever virus transcription[J]. Virus Research, 2013, 173(1):15-28.
[58] Freitas F B, Frouco G, Martins C, et al. In vitro, inhibition of African swine fever virus-topoisomerase Ⅱ disrupts viral replication[J]. Antiviral Research, 2016, 134:34-41.
[59] Alonso C, Galindo I, Cuesta-Geijo M Á, et al. African swine fever virus-cell interactions:From virus entry to cell survival[J]. Virus Research, 2013, 173(1):42-57.
[60] Stefanovic S, Windsor M, Nagata K, et al. Vimentin rearrangement during African swine fever virus infection involves retrograde transport along microtubules and phosphorylation of vimentin by calcium calmodulin kinase Ⅱ[J]. Journal of Virology, 2005, 79(18):11766-11775.
[61] Netherton C L, Wileman T E. African swine fever virus organelle rearrangements[J]. Virus Research, 2013, 173(1):76-86.
[62] Rodríguez J M, García-Escudero R, Salas M L, et al. African swine fever virus structural protein p54 is essential for the recruitment of envelope precursors to assembly sites[J]. Journal of Virology, 2004, 78(8):4299-4313.
[63] Alonso C, Miskin J, Hernáez B, et al. African swine fever virus protein p54 interacts with the microtubular motor complex through direct binding to light-chain dynein[J]. Journal of Virology, 2001, 75(20):9819-9827.
[64] Windsor M, Hawes P, Monaghan P, et al. Mechanism of collapse of endoplasmic reticulum cisternae during African swine fever virus infection[J]. Traffic, 2012, 13(1):30-42.
[65] Galindo I, Viñuela E, Carrascosa A L. Characterization of the African swine fever virus protein p49:A new late structural polypeptide[J]. Journal of General Virology, 2000, 81(1):59-65.
[66] Heath C M, Windsor M, Wileman T. Membrane association facilitates the correct processing of pp220 during production of the major matrix proteins of African swine fever virus[J]. Journal of Virology, 2003, 77(3):1682-1690.
[67] Salas M L, Andrés G. African swine fever virus morphogenesis[J]. Virus Research, 2013, 173(1):29-41.
[68] Hakobyan A, Arabyan E, Avetisyan A, et al. Apigenin inhibits African swine fever virus infection in vitro[J]. Archives of Virology, 2016, 161(12):3445-3453.
[69] Jouvenet N, Monaghan P, Way M, et al. Transport of African swine fever virus from assembly sites to the plasma membrane is dependent on microtubules and conventional kinesin[J]. Journal of Virology, 2004, 78(15):7990-8001.
[70] Andrés G, García-Escudero R, Viñuela E, et al. African swine fever virus structural protein pE120R is essential for virus transport from assembly sites to plasma membrane but not for infectivity[J]. Journal of Virology, 2001, 75(15):6758-6768.
[71] Hernaez B, Escribano J M, Alonso C. Visualization of the African swine fever virus infection in living cells by incorporation into the virus particle of green fluorescent protein-p54 membrane protein chimera[J]. Virology, 2006, 350(1):1-14.