{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T17:47:07Z","timestamp":1793382427195,"version":"4.5.0"},"reference-count":44,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32322081"],"award-info":[{"award-number":["32322081"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32270156"],"award-info":[{"award-number":["32270156"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U21A20256"],"award-info":[{"award-number":["U21A20256"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32573375"],"award-info":[{"award-number":["32573375"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Key Research and Development Program of China","award":["2021YFD1800100"],"award-info":[{"award-number":["2021YFD1800100"]}]},{"name":"the Central Public-interest Scientific Institution Basal Research Fund","award":["Y2025YC123"],"award-info":[{"award-number":["Y2025YC123"]}]},{"name":"Innovation Program of Chinese Academy of Agricultural Sciences","award":["CAAS-CSLPDCP-202401"],"award-info":[{"award-number":["CAAS-CSLPDCP-202401"]}]},{"name":"Innovation Program of Chinese Academy of Agricultural Sciences","award":["CAAS-CSLPDCP-2023002"],"award-info":[{"award-number":["CAAS-CSLPDCP-2023002"]}]},{"name":"Open Project of National Key Laboratory of Veterinary Public Health Safety, China Agricultural University","award":["2024SKLVPHS01"],"award-info":[{"award-number":["2024SKLVPHS01"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>African swine fever (ASF) is an acute, hemorrhagic, and severe infectious disease caused by African swine fever virus (ASFV), posing significant threats to global swine production. ASFV pathogenesis is closely associated with its sophisticated immune evasion strategies. In this study, we demonstrate that ASFV pB318L, a trans-geranylgeranyl-diphosphate synthase (GGPPS) homolog inhibited both the NF-\u03baB signaling pathway and the formation of the NLRP3 inflammasome. Infection with ASFV-intB318L (a recombinant ASFV with pB318L expression inhibition) induced significantly higher levels of IL-1\u03b2 compared to its parent strain ASFV HLJ\/18. Mechanically, pB318L interacts with NEMO to inhibit the interaction between IKK\u03b1 and NEMO, and suppresses the K63-linked ubiquitination of NEMO mediated by TRIM21. In addition, pB318L interacts with the NACHT and LRR domains of NLRP3, which prevents the oligomerization of NLRP3 by suppressing the interaction between NEK7 and NLRP3. Crucially, the immunosuppressive functions of pB318L on both NF-\u03baB signaling pathway and NLRP3 inflammasome activation are independent of its GGPPS enzymatic activity. In conclusion, we presented evidence that ASFV pB318L negatively regulates NF-\u03baB signaling pathway and NLRP3 inflammasome. This study provides critical mechanistic insights into the role of pB318L in ASFV pathogenesis and highlights its potential as a target for the development of antiviral strategies or live-attenuated vaccines against ASF.<\/jats:p>","DOI":"10.1371\/journal.ppat.1013558","type":"journal-article","created":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T17:51:55Z","timestamp":1761155515000},"page":"e1013558","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["African swine fever virus pB318L suppresses inflammatory response by inhibiting NF-\u03baB activation and NLRP3 inflammasome formation"],"prefix":"10.1371","volume":"21","author":[{"given":"Xiaohong","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangqiang","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanyu","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siqi","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiongqiong","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoxia","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangnan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changjiang","family":"Weng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6255-993X","authenticated-orcid":true,"given":"Li","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,10,22]]},"reference":[{"issue":"1","key":"ppat.1013558.ref001","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.virusres.2012.10.020","article-title":"African swine fever virus replication and genomics","volume":"173","author":"LK Dixon","year":"2013","journal-title":"Virus Res"},{"issue":"5","key":"ppat.1013558.ref002","doi-asserted-by":"crossref","first-page":"103","DOI":"10.3390\/v9050103","article-title":"African Swine Fever Virus: A Review","volume":"9","author":"I Galindo","year":"2017","journal-title":"Viruses"},{"issue":"6","key":"ppat.1013558.ref003","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1111\/tbed.12989","article-title":"Emergence of African Swine Fever in China, 2018","volume":"65","author":"X Zhou","year":"2018","journal-title":"Transbound Emerg Dis"},{"issue":"5","key":"ppat.1013558.ref004","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1007\/s12250-019-00173-6","article-title":"Pan-Genomic Analysis of African Swine Fever Virus","volume":"35","author":"Z Wang","year":"2020","journal-title":"Virol Sin"},{"issue":"6465","key":"ppat.1013558.ref005","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1126\/science.aaz1439","article-title":"Architecture of African swine fever virus and implications for viral assembly","volume":"366","author":"N Wang","year":"2019","journal-title":"Science"},{"key":"ppat.1013558.ref006","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.virusres.2019.04.002","article-title":"African swine fever virus evasion of host defences","volume":"266","author":"LK Dixon","year":"2019","journal-title":"Virus Res"},{"issue":"3","key":"ppat.1013558.ref007","doi-asserted-by":"crossref","first-page":"547","DOI":"10.3390\/v14030547","article-title":"A Tug of War: Pseudorabies Virus and Host Antiviral Innate Immunity","volume":"14","author":"G Ye","year":"2022","journal-title":"Viruses"},{"key":"ppat.1013558.ref008","article-title":"Missing pieces in the NF-kappaB puzzle","author":"S Ghosh","year":"2002","journal-title":"Cell"},{"issue":"3","key":"ppat.1013558.ref009","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1002\/wsbm.1331","article-title":"Signaling via the NF\u03baB system","volume":"8","author":"S Mitchell","year":"2016","journal-title":"Wiley Interdiscip Rev Syst Biol Med"},{"key":"ppat.1013558.ref010","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.coviro.2020.10.001","article-title":"Detection of viruses by inflammasomes","volume":"46","author":"L Spel","year":"2021","journal-title":"Curr Opin Virol"},{"issue":"4","key":"ppat.1013558.ref011","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.tibs.2016.10.004","article-title":"Pyroptosis: Gasdermin-Mediated Programmed Necrotic Cell Death","volume":"42","author":"J Shi","year":"2017","journal-title":"Trends Biochem Sci"},{"issue":"14","key":"ppat.1013558.ref012","doi-asserted-by":"crossref","first-page":"9417","DOI":"10.1074\/jbc.272.14.9417","article-title":"African swine fever virus trans-prenyltransferase","volume":"272","author":"A Alejo","year":"1997","journal-title":"J Biol Chem"},{"issue":"1","key":"ppat.1013558.ref013","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1006\/viro.1995.1149","article-title":"Analysis of the complete nucleotide sequence of African swine fever virus","volume":"208","author":"RJ Y\u00e1\u00f1ez","year":"1995","journal-title":"Virology"},{"issue":"25","key":"ppat.1013558.ref014","doi-asserted-by":"crossref","first-page":"18033","DOI":"10.1074\/jbc.274.25.18033","article-title":"The African swine fever virus prenyltransferase is an integral membrane trans-geranylgeranyl-diphosphate synthase","volume":"274","author":"A Alejo","year":"1999","journal-title":"J Biol Chem"},{"issue":"4","key":"ppat.1013558.ref015","article-title":"African swine fever virus pB318L, a trans-geranylgeranyl-diphosphate synthase, negatively regulates cGAS-STING and IFNAR-JAK-STAT signaling pathways","volume":"20","author":"X Liu","year":"2024","journal-title":"PLoS Pathog"},{"issue":"2","key":"ppat.1013558.ref016","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.molp.2015.10.010","article-title":"Structural Analyses of Short-Chain Prenyltransferases Identify an Evolutionarily Conserved GFPPS Clade in Brassicaceae Plants","volume":"9","author":"C Wang","year":"2016","journal-title":"Mol Plant"},{"key":"ppat.1013558.ref017","doi-asserted-by":"crossref","first-page":"108832","DOI":"10.1016\/j.vetmic.2020.108832","article-title":"Multifaceted Immune Responses to African Swine Fever Virus: Implications for Vaccine Development","volume":"249","author":"T Wang","year":"2020","journal-title":"Vet Microbiol"},{"issue":"4","key":"ppat.1013558.ref018","doi-asserted-by":"crossref","first-page":"941","DOI":"10.5455\/OVJ.2024.v14.i4.1","article-title":"African swine fever virus proteins against host antiviral innate immunity and their implications for vaccine development","volume":"14","author":"FL Orosco","year":"2024","journal-title":"Open Vet J"},{"key":"ppat.1013558.ref019","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1146\/annurev-immunol-070119-115052","article-title":"Innate Immune Response to Cytoplasmic DNA: Mechanisms and Diseases","volume":"38","author":"M-M Hu","year":"2020","journal-title":"Annu Rev Immunol"},{"issue":"6","key":"ppat.1013558.ref020","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.cell.2010.01.022","article-title":"Pattern recognition receptors and inflammation","volume":"140","author":"O Takeuchi","year":"2010","journal-title":"Cell"},{"issue":"21","key":"ppat.1013558.ref021","first-page":"2935","article-title":"Modulation of Host Antiviral Innate Immunity by African Swine Fever Virus: A Review","volume":"12","author":"W-R He","year":"2022","journal-title":"Animals (Basel)"},{"issue":"1","key":"ppat.1013558.ref022","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.virol.2013.04.028","article-title":"Deletion of virulence associated genes from attenuated African swine fever virus isolate OUR T88\/3 decreases its ability to protect against challenge with virulent virus","volume":"443","author":"CC Abrams","year":"2013","journal-title":"Virology"},{"issue":"2","key":"ppat.1013558.ref023","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1128\/JVI.72.2.1028-1035.1998","article-title":"A nonessential African swine fever virus gene UK is a significant virulence determinant in domestic swine","volume":"72","author":"L Zsak","year":"1998","journal-title":"J Virol"},{"issue":"12","key":"ppat.1013558.ref024","doi-asserted-by":"crossref","first-page":"8865","DOI":"10.1128\/jvi.70.12.8865-8871.1996","article-title":"An African swine fever virus virulence-associated gene NL-S with similarity to the herpes simplex virus ICP34.5 gene","volume":"70","author":"L Zsak","year":"1996","journal-title":"J Virol"},{"issue":"20","key":"ppat.1013558.ref025","doi-asserted-by":"crossref","first-page":"10681","DOI":"10.1128\/JVI.01027-10","article-title":"The African swine fever virus DP71L protein recruits the protein phosphatase 1 catalytic subunit to dephosphorylate eIF2alpha and inhibits CHOP induction but is dispensable for these activities during virus infection","volume":"84","author":"F Zhang","year":"2010","journal-title":"J Virol"},{"issue":"3","key":"ppat.1013558.ref026","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.bbrc.2018.10.103","article-title":"Inhibition of cGAS-STING-TBK1 signaling pathway by DP96R of ASFV China 2018\/1","volume":"506","author":"X Wang","year":"2018","journal-title":"Biochem Biophys Res Commun"},{"issue":"7","key":"ppat.1013558.ref027","article-title":"pMGF505-7R determines pathogenicity of African swine fever virus infection by inhibiting IL-1\u03b2 and type I IFN production","volume":"17","author":"J Li","year":"2021","journal-title":"PLoS Pathog"},{"issue":"8","key":"ppat.1013558.ref028","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.4049\/jimmunol.2001110","article-title":"African Swine Fever Virus MGF-505-7R Negatively Regulates cGAS-STING-Mediated Signaling Pathway","volume":"206","author":"D Li","year":"2021","journal-title":"J Immunol"},{"issue":"2","key":"ppat.1013558.ref029","doi-asserted-by":"crossref","DOI":"10.1128\/jvi.01227-22","article-title":"Deletion of African Swine Fever Virus (ASFV) H240R Gene Attenuates the Virulence of ASFV by Enhancing NLRP3-Mediated Inflammatory Responses","volume":"97","author":"L Huang","year":"2023","journal-title":"J Virol"},{"issue":"9","key":"ppat.1013558.ref030","article-title":"African Swine Fever Virus H240R Protein Inhibits the Production of Type I Interferon through Disrupting the Oligomerization of STING","volume":"97","author":"G Ye","year":"2023","journal-title":"J Virol"},{"issue":"3","key":"ppat.1013558.ref031","article-title":"African swine fever virus pH240R enhances viral replication via inhibition of the type I IFN signaling pathway","volume":"98","author":"G Ye","year":"2024","journal-title":"J Virol"},{"issue":"10","key":"ppat.1013558.ref032","article-title":"Development of a new effective African swine fever virus vaccine candidate by deletion of the H240R and MGF505-7R genes results in protective immunity against the Eurasia strain","volume":"97","author":"J Li","year":"2023","journal-title":"J Virol"},{"issue":"10","key":"ppat.1013558.ref033","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.3390\/v13102017","article-title":"TNF-Mediated Inhibition of Classical Swine Fever Virus Replication Is IRF1-, NF-\u03baB- and JAK\/STAT Signaling-Dependent","volume":"13","author":"M Liniger","year":"2021","journal-title":"Viruses"},{"key":"ppat.1013558.ref034","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.jneuroim.2008.01.009","article-title":"Japanese Encephalitis Virus infection induces IL-18 and IL-1beta in microglia and astrocytes: correlation with in vitro cytokine responsiveness of glial cells and subsequent neuronal death","volume":"195","author":"S Das","year":"2008","journal-title":"J Neuroimmunol"},{"issue":"5","key":"ppat.1013558.ref035","doi-asserted-by":"crossref","DOI":"10.1128\/mSphere.00658-21","article-title":"African Swine Fever Virus F317L Protein Inhibits NF-\u03baB Activation To Evade Host Immune Response and Promote Viral Replication","volume":"6","author":"J Yang","year":"2021","journal-title":"mSphere"},{"issue":"1","key":"ppat.1013558.ref036","doi-asserted-by":"crossref","first-page":"101480","DOI":"10.1016\/j.jbc.2021.101480","article-title":"African swine fever virus cysteine protease pS273R inhibits pyroptosis by noncanonically cleaving gasdermin D","volume":"298","author":"G Zhao","year":"2022","journal-title":"J Biol Chem"},{"issue":"12","key":"ppat.1013558.ref037","doi-asserted-by":"crossref","first-page":"8527","DOI":"10.1128\/jvi.70.12.8527-8533.1996","article-title":"An IkappaB homolog encoded by African swine fever virus provides a novel mechanism for downregulation of proinflammatory cytokine responses in host macrophages","volume":"70","author":"PP Powell","year":"1996","journal-title":"J Virol"},{"issue":"12","key":"ppat.1013558.ref038","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1016\/S0022-2275(20)41331-8","article-title":"Biochemistry of protein prenylation","volume":"33","author":"PJ Casey","year":"1992","journal-title":"J Lipid Res"},{"issue":"6","key":"ppat.1013558.ref039","doi-asserted-by":"crossref","DOI":"10.1016\/j.jaci.2019.02.013","article-title":"Lack of protein prenylation promotes NLRP3 inflammasome assembly in human monocytes","volume":"143","author":"OP Skinner","year":"2019","journal-title":"J Allergy Clin Immunol"},{"issue":"40","key":"ppat.1013558.ref040","doi-asserted-by":"crossref","first-page":"27757","DOI":"10.1074\/jbc.M114.571810","article-title":"Unprenylated RhoA contributes to IL-1\u03b2 hypersecretion in mevalonate kinase deficiency model through stimulation of Rac1 activity","volume":"289","author":"R van der Burgh","year":"2014","journal-title":"J Biol Chem"},{"key":"ppat.1013558.ref041","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.3389\/fimmu.2019.02049","article-title":"TRIM21-From Intracellular Immunity to Therapy","volume":"10","author":"S Foss","year":"2019","journal-title":"Front Immunol"},{"issue":"4","key":"ppat.1013558.ref042","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/ni.2548","article-title":"Intracellular antibody-bound pathogens stimulate immune signaling via the Fc receptor TRIM21","volume":"14","author":"WA McEwan","year":"2013","journal-title":"Nat Immunol"},{"issue":"32","key":"ppat.1013558.ref043","doi-asserted-by":"crossref","first-page":"10014","DOI":"10.1073\/pnas.1507534112","article-title":"Sequential ubiquitination and deubiquitination enzymes synchronize the dual sensor and effector functions of TRIM21","volume":"112","author":"AJ Fletcher","year":"2015","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"ppat.1013558.ref044","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1080\/22221751.2019.1590128","article-title":"Replication and virulence in pigs of the first African swine fever virus isolated in China","volume":"8","author":"D Zhao","year":"2019","journal-title":"Emerg Microbes Infect"}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1013558","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T17:52:05Z","timestamp":1761155525000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1013558"}},"subtitle":[],"editor":[{"given":"Linda Kathleen","family":"Dixon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,10,22]]},"references-count":44,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10,22]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1013558","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,22]]}}}