{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:12:15Z","timestamp":1791389535208,"version":"4.3.3"},"reference-count":48,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2020,11,1]],"date-time":"2020-11-01T00:00:00Z","timestamp":1604188800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,11,1]],"date-time":"2020-11-01T00:00:00Z","timestamp":1604188800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation","doi-asserted-by":"crossref","award":["31672565"],"award-info":[{"award-number":["31672565"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Key Program of Research and Development of China","award":["2018YFD0500803"],"award-info":[{"award-number":["2018YFD0500803"]}]},{"name":"Jiangsu Key Program of Research and Development for PRRSV","award":["BE2018386"],"award-info":[{"award-number":["BE2018386"]}]},{"name":"Ministry of Agriculture for Swine Disease Control","award":["CARS-36"],"award-info":[{"award-number":["CARS-36"]}]},{"DOI":"10.13039\/501100012246","name":"Priority Academic Program Development of Jiangsu Higher Education Institutions","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100012246","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Veterinary Microbiology"],"published-print":{"date-parts":[[2020,11]]},"DOI":"10.1016\/j.vetmic.2020.108863","type":"journal-article","created":{"date-parts":[[2020,9,29]],"date-time":"2020-09-29T05:44:25Z","timestamp":1601358265000},"page":"108863","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":31,"special_numbering":"C","title":["Porcine reproductive and respiratory syndrome virus Nsp4 cleaves ZAP to antagonize its antiviral activity"],"prefix":"10.1016","volume":"250","author":[{"given":"Yongxiang","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongbao","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuewei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Nauwynck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.vetmic.2020.108863_bib0005","doi-asserted-by":"crossref","first-page":"11555","DOI":"10.1128\/JVI.77.21.11555-11562.2003","article-title":"Expression of the zinc-finger antiviral protein inhibits alphavirus replication","volume":"77","author":"Bick","year":"2003","journal-title":"J. Virol."},{"key":"10.1016\/j.vetmic.2020.108863_bib0010","first-page":"629","article-title":"Nidovirales: a new order comprising Coronaviridae and Arteriviridae","volume":"142","author":"Cavanagh","year":"1996","journal-title":"Arch. Virol."},{"key":"10.1016\/j.vetmic.2020.108863_bib0015","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1128\/JVI.00986-17","article-title":"The nucleocapsid protein and non-structural protein 10 of highly pathogenic porcine reproductive and respiratory syndrome virus enhance CD83 production via NF-\u03baB and Sp1 signaling pathways","volume":"91","author":"Chen","year":"2017","journal-title":"J. Virol."},{"key":"10.1016\/j.vetmic.2020.108863_bib0020","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1007\/s007050050662","article-title":"Current knowledge on the structural proteins of porcine reproductive and respiratory syndrome (PRRS) virus: comparison of the North American and European isolates","volume":"145","author":"Dea","year":"2000","journal-title":"Arch. Virol."},{"key":"10.1016\/j.vetmic.2020.108863_bib0025","doi-asserted-by":"crossref","first-page":"11045","DOI":"10.1128\/JVI.00655-10","article-title":"Porcine reproductive and respiratory syndrome virus inhibits type I interferon signaling by blocking STAT1\/STAT2 nuclear translocation","volume":"84","author":"Deendayal","year":"2010","journal-title":"J. Virol."},{"key":"10.1016\/j.vetmic.2020.108863_bib0030","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.vetmic.2018.08.012","article-title":"Porcine reproductive and respiratory syndrome virus nsp1beta and nsp11 antagonize the antiviral activity of cholesterol-25-hydroxylase via lysosomal degradation","volume":"223","author":"Dong","year":"2018","journal-title":"Vet. Microbiol."},{"key":"10.1016\/j.vetmic.2020.108863_bib0035","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.virusres.2010.07.030","article-title":"The PRRSV replicase: Exploring the multifunctionality of an intriguing set of nonstructural proteins","volume":"154","author":"Fang","year":"2010","journal-title":"Virus Res."},{"key":"10.1016\/j.vetmic.2020.108863_bib0040","doi-asserted-by":"crossref","first-page":"e156513","DOI":"10.1371\/journal.pone.0156513","article-title":"Monkey Viperin Restricts Porcine Reproductive and Respiratory Syndrome Virus Replication","volume":"11","author":"Fang","year":"2016","journal-title":"PLoS One"},{"key":"10.1016\/j.vetmic.2020.108863_bib0045","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1126\/science.1074276","article-title":"Inhibition of retroviral RNA production by ZAP, a CCCH-type zinc finger protein","volume":"297","author":"Gao","year":"2002","journal-title":"Science"},{"key":"10.1016\/j.vetmic.2020.108863_bib0050","doi-asserted-by":"crossref","first-page":"12781","DOI":"10.1128\/JVI.78.23.12781-12787.2004","article-title":"The zinc finger antiviral protein directly binds to specific viral mRNAs through the CCCH zinc finger motifs","volume":"78","author":"Guo","year":"2004","journal-title":"J. Virol."},{"key":"10.1016\/j.vetmic.2020.108863_bib0055","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1073\/pnas.0607063104","article-title":"The zinc-finger antiviral protein recruits the RNA processing exosome to degrade the target mRNA","volume":"104","author":"Guo","year":"2007","journal-title":"Proc. Natl. Acad. Sci."},{"key":"10.1016\/j.vetmic.2020.108863_bib0060","doi-asserted-by":"crossref","first-page":"10934","DOI":"10.1128\/JVI.01396-14","article-title":"Porcine reproductive and respiratory syndrome virus nonstructural protein 4 antagonizes beta interferon expression by targeting the NF- \u03baB essential modulator","volume":"88","author":"Huang","year":"2014","journal-title":"J. Virol."},{"key":"10.1016\/j.vetmic.2020.108863_bib0065","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.virusres.2014.12.014","article-title":"Regulation and evasion of antiviral immune responses by porcine reproductive and respiratory syndrome virus","volume":"202","author":"Huang","year":"2015","journal-title":"Virus Res."},{"key":"10.1016\/j.vetmic.2020.108863_bib0070","doi-asserted-by":"crossref","first-page":"28497","DOI":"10.1038\/srep28497","article-title":"Highly pathogenic porcine reproductive and respiratory syndrome virus Nsp4 Cleaves VISA to impair antiviral responses mediated by RIG-I-like receptors","volume":"6","author":"Huang","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.vetmic.2020.108863_bib0075","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.virol.2015.02.012","article-title":"PRRSV structure, replication and recombination: origin of phenotype and genotype diversity","volume":"479\u2013480","author":"Kappes","year":"2015","journal-title":"Virology"},{"key":"10.1016\/j.vetmic.2020.108863_bib0080","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1128\/JVI.00827-17","article-title":"Cholesterol 25-Hydroxylase inhibits porcine reproductive and respiratory syndrome virus replication through enzyme activity dependent and independent mechanisms","volume":"91","author":"Ke","year":"2017","journal-title":"J. Virol."},{"key":"10.1016\/j.vetmic.2020.108863_bib0085","doi-asserted-by":"crossref","first-page":"e21","DOI":"10.1371\/journal.pgen.0040021","article-title":"Positive selection and increased antiviral activity associated with the PARP-containing isoform of human zinc-finger antiviral protein","volume":"4","author":"Kerns","year":"2008","journal-title":"PLoS Genet."},{"key":"10.1016\/j.vetmic.2020.108863_bib0090","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0378-1119(02)00398-0","article-title":"Signaling through the JAK\/STAT pathway, recent advances and future challenges","volume":"285","author":"Kisseleva","year":"2002","journal-title":"Gene"},{"key":"10.1016\/j.vetmic.2020.108863_bib0095","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1099\/vir.0.039289-0","article-title":"Identification of porcine reproductive and respiratory syndrome virus ORF1a-encoded non-structural proteins in virus-infected cells","volume":"93","author":"Li","year":"2012","journal-title":"J. Gen. Virol."},{"key":"10.1016\/j.vetmic.2020.108863_bib0100","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.virusres.2014.12.027","article-title":"Proteolytic processing of the porcine reproductive and respiratory syndrome virus replicase","volume":"202","author":"Li","year":"2015","journal-title":"Virus Res."},{"key":"10.1016\/j.vetmic.2020.108863_bib0105","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1146\/annurev-animal-022114-111025","article-title":"Porcine reproductive and respiratory syndrome virus (PRRSV): pathogenesis and interaction with the immune system","volume":"4","author":"Lunney","year":"2016","journal-title":"Annu. Rev. Anim. Biosci."},{"key":"10.1016\/j.vetmic.2020.108863_bib0110","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1003494","article-title":"Inhibition of hepatitis B virus replication by the host zinc finger antiviral protein","volume":"9","author":"Mao","year":"2013","journal-title":"PLoS Pathog."},{"key":"10.1016\/j.vetmic.2020.108863_bib0115","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1128\/JVI.01601-06","article-title":"Inhibition of filovirus replication by the zinc finger antiviral protein","volume":"81","author":"Muller","year":"2007","journal-title":"J. Virol."},{"key":"10.1016\/j.vetmic.2020.108863_bib0120","doi-asserted-by":"crossref","first-page":"385","DOI":"10.2460\/javma.2005.227.385","article-title":"Assessment of the economic impact of porcine reproductive and respiratory syndrome on swine production in the United States","volume":"227","author":"Neumann","year":"2005","journal-title":"J. Am. Vet. Med. Assoc."},{"key":"10.1016\/j.vetmic.2020.108863_bib0125","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.immuni.2007.08.012","article-title":"Innate recognition of viruses","volume":"27","author":"Pichlmair","year":"2007","journal-title":"Immunity"},{"key":"10.1016\/j.vetmic.2020.108863_bib0130","doi-asserted-by":"crossref","first-page":"873","DOI":"10.3390\/v7030873","article-title":"Immunological features of the non-structural proteins of porcine reproductive and respiratory syndrome virus","volume":"7","author":"Rasc\u00f3n-Castelo","year":"2015","journal-title":"Viruses"},{"key":"10.1016\/j.vetmic.2020.108863_bib0135","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1146\/annurev-immunol-032713-120231","article-title":"Interferon-stimulated genes: a complex web of host defenses","volume":"32","author":"Schneider","year":"2014","journal-title":"Annu. Rev. Immunol."},{"key":"10.1016\/j.vetmic.2020.108863_bib0140","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.cell.2005.08.012","article-title":"Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-\u03baB and IRF3","volume":"122","author":"Seth","year":"2005","journal-title":"Cell"},{"key":"10.1016\/j.vetmic.2020.108863_bib0145","article-title":"Pathogen recognition and innate immunity","volume":"124","author":"Shizuo","year":"2006","journal-title":"Cell"},{"key":"10.1016\/j.vetmic.2020.108863_bib0150","doi-asserted-by":"crossref","first-page":"4864","DOI":"10.1074\/jbc.271.9.4864","article-title":"The arterivirus nsp4 protease is the prototype of a novel group of chymotrypsin-like enzymes, the 3C-like serine proteases","volume":"271","author":"Snijder","year":"1996","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.vetmic.2020.108863_bib0155","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1099\/vir.0.056341-0","article-title":"Arterivirus molecular biology and pathogenesis","volume":"94","author":"Snijder","year":"2013","journal-title":"J. Gen. Virol."},{"key":"10.1016\/j.vetmic.2020.108863_bib0160","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.vetmic.2017.09.011","article-title":"Cholesterol 25-hydroxylase is an interferon-inducible factor that protects against porcine reproductive and respiratory syndrome virus infection","volume":"210","author":"Song","year":"2017","journal-title":"Vet. Microbiol."},{"key":"10.1016\/j.vetmic.2020.108863_bib0165","doi-asserted-by":"crossref","first-page":"424","DOI":"10.3390\/v4040424","article-title":"Interplay between interferon-mediated innate immunity and porcine reproductive and respiratory syndrome virus","volume":"4","author":"Sun","year":"2012","journal-title":"Viruses"},{"key":"10.1016\/j.vetmic.2020.108863_bib0170","article-title":"IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction","volume":"6","author":"T, K., K, T., S, S., C, C., H, K., H, K., KJ, I., O, T., S, A","year":"2005","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.vetmic.2020.108863_bib0175","doi-asserted-by":"crossref","first-page":"2345","DOI":"10.4049\/jimmunol.1701773","article-title":"Porcine reproductive and respiratory syndrome virus nonstructural protein 4 cleaves porcine DCP1a to attenuate its antiviral activity","volume":"201","author":"Tao","year":"2018","journal-title":"J. Immunol."},{"key":"10.1016\/j.vetmic.2020.108863_bib0180","doi-asserted-by":"crossref","first-page":"e526","DOI":"10.1371\/journal.pone.0000526","article-title":"Emergence of fatal PRRSV variants: unparalleled outbreaks of atypical PRRS in China and molecular dissection of the unique hallmark","volume":"2","author":"Tian","year":"2007","journal-title":"PLoS One"},{"key":"10.1016\/j.vetmic.2020.108863_bib0185","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/j.jmb.2009.07.062","article-title":"Structure and cleavage specificity of the chymotrypsin-like serine protease (3CLSP\/nsp4) of porcine reproductive and respiratory syndrome virus (PRRSV)","volume":"392","author":"Tian","year":"2009","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.vetmic.2020.108863_bib0190","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.virusres.2014.07.025","article-title":"Porcine reproductive and respiratory syndrome virus counteracts the porcine intrinsic virus restriction factors-IFITM1 and Tetherin in MARC-145 cells","volume":"191","author":"Wang","year":"2014","journal-title":"Virus Res."},{"key":"10.1016\/j.vetmic.2020.108863_bib0195","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1089\/jir.2015.0077","article-title":"The interferon-induced Mx2 inhibits porcine reproductive and respiratory syndrome virus replication","volume":"36","author":"Wang","year":"2016","journal-title":"J. Interferon Cytokine Res."},{"key":"10.1016\/j.vetmic.2020.108863_bib0200","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.virusres.2004.04.015","article-title":"Characterization of heteroclite subgenomic RNAs associated with PRRSV infection","volume":"105","author":"Yuan","year":"2004","journal-title":"Virus Res."},{"key":"10.1016\/j.vetmic.2020.108863_bib0205","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1007\/s12275-013-3431-z","article-title":"Overview: replication of porcine reproductive and respiratory syndrome virus","volume":"51","author":"Yun","year":"2013","journal-title":"J. Microbiol."},{"key":"10.1016\/j.vetmic.2020.108863_bib0210","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.antiviral.2013.06.004","article-title":"Poly(I:C) inhibits porcine reproductive and respiratory syndrome virus replication in MARC-145 cells via activation of IFIT3","volume":"99","author":"Zhang","year":"2013","journal-title":"Antiviral Res."},{"key":"10.1016\/j.vetmic.2020.108863_bib0215","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.vetmic.2016.11.010","article-title":"Pathogenicity and antigenicity of a novel NADC30-like strain of porcine reproductive and respiratory syndrome virus emerged in China","volume":"197","author":"Zhang","year":"2016","journal-title":"Vet. Microbiol."},{"key":"10.1016\/j.vetmic.2020.108863_bib0220","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.vetmic.2017.07.028","article-title":"A novel recombinant porcine reproductive and respiratory syndrome virus with significant variation in cell adaption and pathogenicity","volume":"208","author":"Zhang","year":"2017","journal-title":"Vet. Microbiol."},{"key":"10.1016\/j.vetmic.2020.108863_bib0225","doi-asserted-by":"crossref","DOI":"10.1128\/JVI.00001-19","article-title":"ZAP, a CCCH-Type zinc finger protein, inhibits porcine reproductive and respiratory syndrome virus replication and interacts with viral Nsp9","volume":"93","author":"Zhao","year":"2019","journal-title":"J. Virol."},{"key":"10.1016\/j.vetmic.2020.108863_bib0230","doi-asserted-by":"crossref","first-page":"65","DOI":"10.4161\/rna.5.2.6044","article-title":"ZAP-mediated mRNA degradation","volume":"5","author":"Zhu","year":"2008","journal-title":"RNA Biol."},{"key":"10.1016\/j.vetmic.2020.108863_bib0235","doi-asserted-by":"crossref","first-page":"15834","DOI":"10.1073\/pnas.1101676108","article-title":"Zinc-finger antiviral protein inhibits HIV-1 infection by selectively targeting multiply spliced viral mRNAs for degradation","volume":"108","author":"Zhu","year":"2011","journal-title":"Proc. Natl. Acad. Sci."},{"key":"10.1016\/j.vetmic.2020.108863_bib0240","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1099\/0022-1317-81-4-853","article-title":"Virus-encoded proteinases and proteolytic processing in the Nidovirales","volume":"81","author":"Ziebuhr","year":"2000","journal-title":"J. Gen. Virol."}],"container-title":["Veterinary Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0378113520310014?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0378113520310014?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T23:10:51Z","timestamp":1759878651000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0378113520310014"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11]]},"references-count":48,"alternative-id":["S0378113520310014"],"URL":"https:\/\/doi.org\/10.1016\/j.vetmic.2020.108863","relation":{},"ISSN":["0378-1135"],"issn-type":[{"value":"0378-1135","type":"print"}],"subject":[],"published":{"date-parts":[[2020,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Porcine reproductive and respiratory syndrome virus Nsp4 cleaves ZAP to antagonize its antiviral activity","name":"articletitle","label":"Article Title"},{"value":"Veterinary Microbiology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.vetmic.2020.108863","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"108863"}}