非洲猪瘟病毒免疫及基因工程疫苗研究进展

doi:10.16431/j.cnki.1671-7236.2019.11.031

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）引起家猪的一种急性、出血性、高度接触性蜱传病毒病，可致家猪网状内皮系统出血及高死亡率，是危害世界养猪业健康发展最严重的传染病之一。ASFV是一种大型的DNA病毒，结构复杂，其基因组编码大量蛋白。该论文介绍了ASFV的特性，免疫应答机制如免疫逃逸、体液免疫和细胞免疫，以及基因工程疫苗如减毒活疫苗、亚单位疫苗、病毒载体活疫苗及DNA疫苗研究的最新进展，并对中国ASF的疫苗研制、防控进行了展望。

关键词: 非洲猪瘟病毒(ASFV); 细胞凋亡; 自噬; 免疫应答; 基因工程疫苗

Abstract: African swine fever (ASF) is an acute,hemorrhagic and highly contagious tiboviral disease in domestic pigs,caused by African swine fever virus (ASFV).The disease shows reticuloendothelial hemorrhage and high mortality,is one of arguably the most significant emerging disease threat for the swine industry worldwide.ASFV is a large DNA virus,with the complexity of the structure and the large number of proteins encoded by its genome.This review focuses on recent progress of the ASFV characteristics,mechanisms of immune response including immune escape,humoral immunity,and cellular immunity,genetic engineering vaccines including live attenuated vaccines,subunit vaccines,live virus vector vaccines and DNA vaccines.Finally,the vaccine development and prevention and control-eradiction strategies of ASF in China are prospected.

Key words: African swine fever virus (ASFV); apoptosis; autophagy; immune response; genetic engineering vaccines

中图分类号:

S852.65⁺1

马兴树, 宋金祥. 非洲猪瘟病毒免疫及基因工程疫苗研究进展[J]. 中国畜牧兽医, 2019, 46(11): 3404-3413.

MA Xingshu, SONG Jinxiang. Research Progress on Immune Response and Genetic Engineering Vaccines Against African Swine Fever Virus[J]. China Animal Husbandry and Veterinary Medicine, 2019, 46(11): 3404-3413.

参考文献

[1] 王清华,任炜杰,包静月,等.我国首例非洲猪瘟的确诊[J].中国动物检疫,2018,35(9):1-4. WANG Q H,REN W J,BAO J Y,et al.The first outbreak of African swine fever was confirmed in China[J].China Animal Health Inspection,2018,35(9):1-4.(in Chinese)
[2] ALONSO C,BORCA M,DIXON L,et al.ICTV virus taxonomy profile:Asfarviridae[J].Journal of General Viralology,2018,99(5):613-614.
[3] ANDREANI J,KHALIL J Y B,SEVVANA M,et al.Pacmanvirus,a new giant icosahedral virus at the crossroads between Asfarviridae and Faustoviruses[J].Journal of Virolology,2017,91(14):e00212-17.
[4] SALAS M L,ANDRES G.African swine fever virus morphogenesis[J].Virus Research,2013,173(1):29-41.
[5] 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 Viralology,2008,89(Pt2):397-408.
[6] QUEMBO C J,JORI F,VOSLOO W,et al.Genetic characterization of African swine fever virus isolates from soft ticks at the wildlife/domestic interface in Mozambique and identification of a novel genotype[J].Transboundary and Emerging Diseases,2018,65(2):420-431.
[7] CASJENS S.Evolution of the linear DNA replicons of the Borrelia spirochetes[J].Current Opinion in Microbiology,1999,2(5):529-534.
[8] CHEN Z,XU X,WANG Y,et al.DNA segments of African swine fever virus detected for the first time in hard ticks from sheep and bovines[J].Systematic & Applied Acarology,2019,24(1):180-184.
[9] DIXON L K,CHAPMAN D A G,NETHERTON C L,et al.African swine fever virus replication and genomics[J].Virus Reseach,2013,173(1):3-14.
[10] SUAREZ C,SALAS M L,RODRIGUEZ J M.African swine fever virus polyprotein pp62 is essential for viral core development[J].Journal of Virolology,2010,84(1):176-187.
[11] COBBOLD C,WINDSOR M,WILEMAN T.A virally encoded chaperone specialized for folding of the major capsid protein of African swine fever virus[J].Journal of Virolology,2001,75(16):7221-7229.
[12] CHEN Y,LIU H,YANG C,et al.Structure of the error-prone DNA ligase of African swine fever virus identifies critical active site residues[J].Nature Communications,2019,10(1):387.
[13] GALINDO I,ALONSO C.African swine fever virus:A review[J].Viruses,2017,9(5):103-115.
[14] BENEDICT C A,NORRIS P S,WARE C F.To kill or be killed:Viral evasion of apoptosis[J].Nature Immunology,2002,3(11):1013-1018.
[15] BRUN A,RIVAS C,ESTEBAN M,et al.African swine fever virus gene a179l,a viral homologue of BCL-2,protects cells from programmed cell death[J].Virology,1996,225(1):227-230.
[16] GALINDO I,HERNAEZ B,DIAZ-GIL G,et al.A179L,a viral BCL-2 homologue,targets the core BCL-2 apoptotic machinery and its upstream BH3 activators with selective binding restrictions for bid and noxa[J].Virology,2008,375(2):561-572.
[17] RODRIGUEZ C I,NOGAL M L,CARRASCOSA A L,et al.African swine fever virus IAP-like protein induces the activation of nuclear factor kappa B[J]. Journal of Virolology,2002,76(8):3936-3942.
[18] 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.
[19] KLIONSKY D J.Autophagy revisited:A conversation with Christian de Duve[J].Autophagy,2008,4(6):740-743.
[20] RIVERA J,ABRAMS C,HERNAEZ B,et al.The MyD116 African swine fever virus homologue interacts with the catalytic subunit of protein phosphatase 1 and activates its phosphatase activity[J].Journal of Virolology,2007,81(6):2923-2929.
[21] KING K,CHAPMAN D,ARGILAGUET J M,et al.Protection of European domestic pigs from virulent African isolates of African swine fever virus by experimental immunisation[J].Vaccine,2011,29(28):4593-4600.
[22] 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.
[23] ALFONSO P,RIVERA J,HERN B,et al.Identification of cellular proteins modified in response to African swine fever virus infection by proteomics[J].Proteomics,2004,4(7):2037-2046.
[24] SANCHEZ E G,QUINTAS A,NOGAL M,et al.African swine fever virus controls the host transcription and cellular machinery of protein synthesis[J].Virus Research,2013,173(1):58-75.
[25] CORREIA S,VENTURA S,PARKHOUSE R M.Identification and utility of innate immune system evasion mechanisms of ASFV[J].Virus Research,2013,173(1):87-100.
[26] ZSAK L,CALER E,LU Z,et al.A nonessential African swine fever virus gene UK is a significant virulence determinant in domestic swine[J].Journal of Virology,1998,72(2):1028-1035.
[27] BORCA M V,CARRILLO C,ZSAK L,et al.Deletion of a CD2-like gene,8-DR,from African swine fever virus affects viral infection in domestic swine[J]. Journal of Virology,1998,72(4):2881-2889.
[28] BURMAKINA G,MALOGOLOVKIN A,TULMAN E R,et al.African swine fever virus serotype-specific proteins are significant protective antigens for African swine fever[J].Journal of General Virology,2016,97(7):1670-1675.
[29] KOLINBERGER S D,GUTIERREZ-CASTANEDA B,FOSTER-CUEVAS M,et al.Identification of the principal serological immunodeterminants of African swine fever virus by screening a virus cDNA library with antibody[J].Journal of General Virology,2002,83(6):1331-1342.
[30] PENRITH M L,THOMSON G R,BASTOS A D S,et al.An investigation into natural resistance to African swine fever in domestic pigs from an endemic area in southern Africa[J].Scientific and Technical Review of the Office International des Epizooties (Paris),2004,23(3):965-977.
[31] ONISK D V,BORCA M V,KUTISH G,et al.Passively transferred African swine fever virus antibodies protect swine against lethal infection[J].Virology,1994,198(1):350-354.
[32] 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.
[33] TAKAMATSU H H,DENYER M S,LACASTA A,et al.Cellular immunity in ASFV responses[J].Virus Research,2013,173(1):110-121.
[34] OURA C A,DENYER M S,TAKAMATSU H,et al.In vivo depletion of CD8⁺ T lymphocytes abrogates protective immunity to African swine fever virus[J].Journal of General Virology,2005,86(Pt9):2445-2450.
[35] ARGILAGUET J M,PEREZ-MARTIN E,NOFRARIAS M,et al.DNA vaccination partially protects against African swine fever virus lethal challenge in the absence of antibodies[J].PLoS One,2012,7(9):e40942.
[36] JEMSON J S,CHILDERSTONE A,TAKAMATSU H,et al.The cellular immune recognition of proteins expressed by an African swine fever virus random genomic library[J].Journal of Immunological Methods,2000,242(1-2):33-42.
[37] BLOME S,GABRIEL C,BEER M.Modern adjuvants do not enhance the efficacy of an inactivated African swine fever virus vaccine preparation[J].Vaccine,2014,32(31):3879-3882.
[38] SANCHEZ-VIZCAINO J M,MUR L,MARTINEZ-LOPEZ B.African swine fever:An epidemiological update[J].Transboundary Emerging Diseases,2012,59(s1):27-35.
[39] ARIAS M,TORRE A D L,DIXON L,et al.Approaches and perspectives for development of African swine fever virus vaccines[J].Vaccines,2017,5(4):E35.
[40] AFONSO C L,ZSAK L,CARRILLO C,et al.African swine fever virus NL gene is not required for virus virulence[J].Journal of General Virology,1998,79(Pt10):2543-2547.
[41] LEWIS T,ZSAK L,BURRAGE T G,et al.An African swine fever virus ERV1-ALR homologue,9GL,affects virion maturation and viral growth in macrophages and viral virulence in swine[J]. Journal of Virology,2000,74(3):1275-1285.
[42] 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):291-305.
[43] SALGUERO F J,GIL S,REVILLA Y,et al.Cytokine mRNA expression and pathological findings in pigs inoculated with African swine fever virus (E-70) deleted on A238L[J].Veterinary Immunology and Immunopathology,2008,124(1-2):107-119.
[44] GOMEZ-PUERTAS P,RODRIGUEZ F,OVIEDO J M,et al.The African swine fever virus proteins p54 and p30 are involved in two distinct steps of virus attachment and both contribute to the antibody-mediated protective immune response[J].Virology,1998,243(2):461-471.
[45] IVANOV V,EFREMOV E E,NOVIKOV B V,et al.Vaccination with viral protein-mimicking peptides postpones mortality in domestic pigs infected by African swine fever virus[J].Molecular Medicine Reports,2011,4(3):395-401.
[46] RUIZ-GONZALVO F,RODRIGUEZ F,ESCRIBANO J M.Functional and immunological properties of the baculovirus-expressed hemagglutinin of African swine fever virus[J].Virology,1996,218(1):285-289.
[47] LOKHANDWALA S,WAGHELA S D,BRAY J,et al.Induction of Robust immune responses in swine by using a cocktail of adenovirus-vectored African swine fever virus antigens[J].Clinical and Vaccine Immunology,2016,23(11):888-900.
[48] LOPERA-MADRID J,OSORIO J E,HE Y,et al.Safety and immunogenicity of mammalian cell derived and Modified Vaccinia Ankara vectored African swine fever subunit antigens in swine[J].Veterinary Immunology and Immunopathology,2017,185(3):20-33.
[49] LOKHANDWALA S,WAGHELA S D,BRAY J,et al.Adenovirus-vectored novel African swine fever virus antigens elicit robust immune responses in swine[J].PloS One,2017,12(5):e0177007.
[50] ARGILAGUET J M,PEREZ-MARTIN E,GALLARDO C,et al.Enhancing DNA immunization by targeting ASFV antigens to SLA-Ⅱ bearing cells[J].Vaccine,2011,29(33):5379-5385.
[51] PEREZ-NUNEZ D,SUNWOO S Y,SANCHEZ E,et al.Evaluation of a viral DNA-protein immunization strategy against African swine fever in domestic pigs[J].Veterinary Immunology and Immunopathology,2019,208(1):34-43.
[52] MONTGOMERY R E.On a form of swine fever occurring in British east Africa(Kenya colony)[J].Journal of Comparative Pathology and Therapeutics,1921,34(3):159-191.