{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T12:45:59Z","timestamp":1793709959215,"version":"4.6.1"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T00:00:00Z","timestamp":1713398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The whole-genome sequence of an African swine fever virus (ASFV) strain (HuB\/HH\/2019) isolated from Hubei, China, was highly similar to that of the Georgia 2007\/1 strain ASFV. After infection with strong strains, domestic pigs show typical symptoms of infection, including fever, depression, reddening of the skin, hemorrhagic swelling of various tissues, and dysfunction. The earliest detoxification occurred in pharyngeal swabs at 4 days post-infection. The viral load in the blood was extremely high, and ASFV was detected in multiple tissues, with the highest viral loads in the spleen and lungs. An imbalance between pro- and anti-inflammatory factors in the serum leads to an excessive inflammatory response in the body. Immune factor expression is suppressed without effectively eliciting an immune defense. Antibodies against p30 were not detected in acutely dead domestic pigs. Sequencing of the peripheral blood mononuclear cell transcriptome revealed elevated transcription of genes associated with immunity, defense, and stress. The massive reduction in lymphocyte counts in the blood collapses the body\u2019s immune system. An excessive inflammatory response with a massive reduction in the lymphocyte count may be an important cause of mortality in domestic pigs. These two reasons have inspired researchers to reduce excessive inflammatory responses and stimulate effective immune responses for future vaccine development.<\/jats:p>","DOI":"10.3389\/fimmu.2024.1361531","type":"journal-article","created":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T13:20:21Z","timestamp":1713446421000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["Infection of domestic pigs with a genotype II potent strain of ASFV causes cytokine storm and lymphocyte mass reduction"],"prefix":"10.3389","volume":"15","author":[{"given":"Xuezhi","family":"Zuo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guorui","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjie","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qizu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangtao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingju","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yebing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haidong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingqi","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,4,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaz1439","article-title":"Architecture of African swine fever virus and implications for viral assembly","volume":"366","author":"Wang","year":"2019","journal-title":"Science"},{"key":"B2","doi-asserted-by":"publisher","first-page":"10.1128\/jvi.01293-18","DOI":"10.1128\/JVI.01293-18","article-title":"A proteomic atlas of the African swine fever virus particle","volume":"92","author":"Alejo","year":"2018","journal-title":"J Virol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1007\/s00705-002-0946-8","article-title":"Genotyping field strains of African swine fever virus by partial p72 gene characterisation","volume":"148","author":"Bastos","year":"2003","journal-title":"Arch Virol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1111\/tbed.12700","article-title":"Genetic characterization of African swine fever virus isolates from soft ticks at the wildlife\/domestic interface in Mozambique and identification of a novel genotype","volume":"65","author":"Quembo","year":"2018","journal-title":"Transbound Emerg Dis"},{"key":"B5","doi-asserted-by":"publisher","first-page":"574","DOI":"10.3390\/v15020574","article-title":"Antagonisms of ASFV towards host defense mechanisms: knowledge gaps in viral immune evasion and pathogenesis","volume":"15","author":"Yu","year":"2023","journal-title":"Viruses"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1186\/s13567-022-01025-0","article-title":"African swine fever virus MGF360-11L negatively regulates cGAS-STING-mediated inhibition of Type I interferon production","volume":"53","author":"Yang","year":"2022","journal-title":"Vet Res"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.818969","article-title":"African swine fever virus MGF360-14L negatively regulates Type I interferon signaling by targeting IRF3","volume":"11","author":"Wang","year":"2021","journal-title":"Front Cell Infect Microbiol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2100320","article-title":"African swine fever virus pI215L negatively regulates cGAS-STING signaling pathway through recruiting RNF138 to inhibit K63-linked ubiquitination of TBK1","volume":"207","author":"Huang","year":"2021","journal-title":"J Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2021.722952","article-title":"African swine fever virus induces STAT1 and STAT2 degradation to counteract IFN-I signaling","volume":"12","author":"Riera","year":"2021","journal-title":"Front Microbiol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.02330-21","article-title":"MGF360-9L is a major virulence factor associated with the African swine fever virus by antagonizing the JAK\/STAT signaling pathway","volume":"13","author":"Zhang","year":"2022","journal-title":"mBio"},{"key":"B11","doi-asserted-by":"publisher","first-page":"2046","DOI":"10.3390\/v13102046","article-title":"African swine fever virus A528R inhibits TLR8 mediated NF-\u03baB activity by targeting p65 activation and nuclear translocation","volume":"13","author":"Liu","year":"2021","journal-title":"Viruses"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1007\/s12250-020-00304-4","article-title":"African swine fever virus MGF360-12L inhibits Type I interferon production by blocking the interaction of importin \u03b1 and NF-\u03baB signaling pathway","volume":"36","author":"Zhuo","year":"2021","journal-title":"Virol Sin"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2017.02.002","article-title":"Identification of residues within the African swine fever virus DP71L protein required for dephosphorylation of translation initiation factor eIF2\u03b1 and inhibiting activation of pro-apoptotic CHOP","volume":"504","author":"Barber","year":"2017","journal-title":"Virology"},{"key":"B14","doi-asserted-by":"publisher","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":"Powell","year":"1996","journal-title":"J Virol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.74.20.9412-9420.2000","article-title":"African swine fever virus protein A238L interacts with the cellular phosphatase calcineurin via a binding domain similar to that of NFAT","volume":"74","author":"Miskin","year":"2000","journal-title":"J Virol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.00329-22","article-title":"Combinational deletions of MGF360-9L and MGF505-7R attenuated highly virulent African swine fever virus and conferred protection against homologous challenge","volume":"96","author":"Ding","year":"2022","journal-title":"J Virol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01139-21","article-title":"Deletion of the A137R gene from the pandemic strain of African swine fever virus attenuates the strain and offers protection against the virulent pandemic virus","volume":"95","author":"Gladue","year":"2021","journal-title":"J Virol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1834","DOI":"10.3390\/v14081834","article-title":"ASFV gene A151R is involved in the process of virulence in domestic swine","volume":"14","author":"Ramirez-Medina","year":"2022","journal-title":"Viruses"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2012.11.009","article-title":"Cellular immunity in ASFV responses","volume":"173","author":"Takamatsu","year":"2013","journal-title":"Virus Res"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a118408","article-title":"A simple method of estimating fifty per cent endpoints","volume":"27","author":"Reed","year":"1938","journal-title":"Am J Epidemiol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1111\/tbed.14222","article-title":"Dynamics of African swine fever virus (ASFV) infection in domestic pigs infected with virulent, moderate virulent and attenuated genotype II ASFV European isolates","volume":"68","author":"Gallardo","year":"2021","journal-title":"Transbound Emerg Dis"},{"key":"B22","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1186\/s12985-023-02111-1","article-title":"A quadruple fluorescence quantitative PCR method for the identification of wild strains of african swine fever and gene-deficient strains","volume":"20","author":"Zuo","year":"2023","journal-title":"Virol J"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1186\/s13567-014-0093-8","article-title":"Dynamics of African swine fever virus shedding and excretion in domestic pigs infected by intramuscular inoculation and contact transmission","volume":"45","author":"Guinat","year":"2014","journal-title":"Vet Res"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2016.08.011","article-title":"Deletion of African swine fever virus interferon inhibitors from the genome of a virulent isolate reduces virulence in domestic pigs and induces a protective response","volume":"34","author":"Reis","year":"2016","journal-title":"Vaccine"},{"key":"B25","doi-asserted-by":"publisher","first-page":"10.1128\/jvi.00350-20","DOI":"10.1128\/JVI.00350-20","article-title":"Absence of long-term protection in domestic pigs immunized with attenuated african swine fever virus isolate OURT88\/3 or Benin\u0394MGF correlates with increased levels of regulatory T cells and interleukin-10","volume":"94","author":"S\u00e1nchez-Cord\u00f3n","year":"2020","journal-title":"J Virol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3201\/eid2411.181274","article-title":"Molecular characterization of African swine fever virus, China, 2018","volume":"24","author":"Ge","year":"2018","journal-title":"Emerg Infect Dis"},{"key":"B27","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.virusres.2018.10.007","article-title":"Infection, modulation and responses of antigen-presenting cells to African swine fever viruses","volume":"258","author":"Franzoni","year":"2018","journal-title":"Virus Res"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-79-6-1427","article-title":"African swine fever: a disease characterized by apoptosis","volume":"79","author":"Oura","year":"1998","journal-title":"J Gen Virol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1038\/nri.2016.123","article-title":"Cytokine networks in neuroinflammation","volume":"17","author":"Becher","year":"2017","journal-title":"Nat Rev Immunol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0131-x","article-title":"Cytokine-mediated communication: a quantitative appraisal of immune complexity","volume":"19","author":"Altan-Bonnet","year":"2019","journal-title":"Nat Rev Immunol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/nbt0518-378","article-title":"Cytokine resurrection: engineered IL-2 ramps up immuno-oncology responses","volume":"36","author":"Garber","year":"2018","journal-title":"Nat Biotechnol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3389\/fvets.2020.601641","article-title":"Cytokine storm in domestic pigs induced by infection of virulent african swine fever virus","volume":"7","author":"Wang","year":"2020","journal-title":"Front Vet Sci"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3389\/fvets.2020.601641","article-title":"Cytokine storm","volume":"383","author":"Fajgenbaum","year":"2020","journal-title":"N Engl J Med"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1089\/jir.2020.0213","article-title":"Cytokines in febrile diseases","volume":"41","author":"Lai","year":"2021","journal-title":"J Interferon Cytokine Res"},{"key":"B35","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1097\/00005792-195012000-00003","article-title":"The properties and biologic effects of bacterial pyrogens","volume":"29","author":"Bennett","year":"1950","journal-title":"Medicine"},{"key":"B36","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1084\/jem.103.5.589","article-title":"Temperature-elevating effect of a substance obtained from polymorphonuclear leucocytes","volume":"27","author":"Beeson","year":"1948","journal-title":"J Clin Invest"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-60761-421-0_7","article-title":"Generation of stable Th1\/CTL-, Th2-, and Th17-inducing human dendritic cells","volume":"595","author":"Kalinski","year":"2010","journal-title":"Methods Mol Biol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1002\/eji.201141753","article-title":"Deficient CCR7 signaling promotes TH2 polarization and B-cell activation in vivo","volume":"42","author":"Moschovakis","year":"2012","journal-title":"Eur J Immunol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2017.12.030","article-title":"Evaluation of protection induced by immunisation of domestic pigs with deletion mutant African swine fever virus Benin\u0394MGF by different doses and routes","volume":"36","author":"S\u00e1nchez-Cord\u00f3n","year":"2018","journal-title":"Vaccine"},{"key":"B40","doi-asserted-by":"publisher","first-page":"291","DOI":"10.3390\/v8100291","article-title":"Association of the host immune response with protection using a live attenuated african swine fever virus model","volume":"8","author":"Carlson","year":"2016","journal-title":"Viruses"},{"key":"B41","doi-asserted-by":"publisher","first-page":"10.1128\/jvi.01760-16","DOI":"10.1128\/JVI.01760-16","article-title":"Simultaneous deletion of the 9GL and UK genes from the african swine fever virus Georgia 2007 isolate offers increased safety and protection against homologous challenge","volume":"91","author":"O'Donnell","year":"2017","journal-title":"J Virol"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.antiviral.2016.11.021","article-title":"Different routes and doses influence protection in pigs immunised with the naturally attenuated African swine fever virus isolate OURT88\/3","volume":"138","author":"S\u00e1nchez-Cord\u00f3n","year":"2017","journal-title":"Antiviral Res"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetimm.2011.12.013","article-title":"Interferon status and white blood cells during infection with African swine fever virus in vivo","volume":"145","author":"Karalyan","year":"2012","journal-title":"Veterinary Immunol immunopathology"},{"key":"B44","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1089\/vim.2016.0121","article-title":"Influence of age and dose of african swine fever virus infections on clinical outcome and blood parameters in pigs","volume":"30","author":"Post","year":"2017","journal-title":"Viral Immunol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"10.1128\/jvi.01428-17","DOI":"10.1128\/JVI.01428-17","article-title":"Deletion of the African Swine Fever Virus Gene DP148R Does Not Reduce Virus Replication in Culture but Reduces Virus Virulence in Pigs and Induces High Levels of Protection against Challenge","volume":"91","author":"Reis","year":"2017","journal-title":"J Virol"},{"key":"B46","doi-asserted-by":"publisher","first-page":"262","DOI":"10.3390\/vaccines8020262","article-title":"Deletion of the gene for the type I interferon inhibitor I329L from the attenuated african swine fever virus OURT88\/3 strain reduces protection induced in pigs","volume":"8","author":"Reis","year":"2020","journal-title":"Vaccines"},{"key":"B47","doi-asserted-by":"publisher","first-page":"2003","DOI":"10.3390\/v14092003","article-title":"Host responses to live-attenuated ASFV (HLJ\/18-7GD)","volume":"14","author":"Fan","year":"2022","journal-title":"Viruses"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.00577-23","article-title":"African swine fever virus H240R protein inhibits the production of type I interferon through disrupting the oligomerization of STING","volume":"97","author":"Ye","year":"2023","journal-title":"J Virol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2023.199190","article-title":"African swine fever virus pF778R attenuates type I interferon response by impeding STAT1 nuclear translocation","volume":"335","author":"Chen","year":"2023","journal-title":"Virus Res"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.01203","article-title":"Inhibition of african swine fever virus replication by porcine type I and type II interferons","volume":"11","author":"Fan","year":"2020","journal-title":"Front Microbiol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00491","article-title":"Macrophage cytokines: involvement in immunity and infectious diseases","volume":"5","author":"Arango Duque","year":"2014","journal-title":"Front Immunol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2366","article-title":"IL-12 family cytokines: immunological playmakers","volume":"13","author":"Vignali","year":"2012","journal-title":"Nat Immunol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2010.164","article-title":"Mini-review series: focus on chemokines","volume":"89","author":"Comerford","year":"2011","journal-title":"Cell Immunol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1007\/s10439-014-1242-y","article-title":"Immobilized IL-8 triggers phagocytosis and dynamic changes in membrane microtopology in human neutrophils","volume":"43","author":"Beste","year":"2015","journal-title":"Ann Biomed Eng"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1186\/1297-9716-44-87","article-title":"Increase in chemokines CXCL10 and CCL2 in blood from pigs infected with high compared to low virulence African swine fever virus isolates","volume":"44","author":"Fishbourne","year":"2013","journal-title":"Vet Res"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1007\/s00705-015-2401-7","article-title":"A study of lymphoid organs and serum proinflammatory cytokines in pigs infected with African swine fever virus genotype II","volume":"160","author":"Zakaryan","year":"2015","journal-title":"Arch Virol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010522","article-title":"The baseline immunological and hygienic status of pigs impact disease severity of African swine fever","volume":"18","author":"Radulovic","year":"2022","journal-title":"PloS Pathog"},{"key":"B58","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1186\/s12985-021-01637-6","article-title":"Mechanism of interaction between virus and host is inferred from the changes of gene expression in macrophages infected with African swine fever virus CN\/GS\/2018 strain","volume":"18","author":"Yang","year":"2021","journal-title":"Virol J"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1616998114","article-title":"Structure and activation of C1, the complex initiating the classical pathway of the complement cascade","volume":"114","author":"Mortensen","year":"2017","journal-title":"Proc Natl Acad Sci U.S.A"},{"key":"B60","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1146\/annurev-immunol-032713-120145","article-title":"Chemokines and chemokine receptors: Positioning cells for host defense and immunity","volume":"32","author":"Griffith","year":"2014","journal-title":"Annu Rev Immunol"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.3390\/ani12212935","article-title":"Modulation of host antiviral innate immunity by african swine fever virus: A review","volume":"12","author":"He","year":"2022","journal-title":"Anim (Basel)"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.3.2173-2180.1999","article-title":"African swine fever virus infection induces tumor necrosis factor alpha production: implications in pathogenesis","volume":"73","author":"G\u00f3mez del Moral","year":"1999","journal-title":"J Virol"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.68.1.580-583.1994","article-title":"Long-term persistent infection of swine monocytes\/macrophages with African swine fever virus","volume":"68","author":"Carrillo","year":"1994","journal-title":"J Virol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1361531\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T13:20:25Z","timestamp":1713446425000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1361531\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,18]]},"references-count":63,"alternative-id":["10.3389\/fimmu.2024.1361531"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2024.1361531","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,18]]},"article-number":"1361531"}}