{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T09:07:51Z","timestamp":1769072871123,"version":"3.49.0"},"reference-count":21,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T00:00:00Z","timestamp":1682640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chinese National Natural Science Foundation","award":["82171813"],"award-info":[{"award-number":["82171813"]}]},{"name":"Chinese National Natural Science Foundation","award":["KJ2021A0835"],"award-info":[{"award-number":["KJ2021A0835"]}]},{"name":"Chinese National Natural Science Foundation","award":["BXQN202105"],"award-info":[{"award-number":["BXQN202105"]}]},{"name":"the Priority Academic Program Development of Jiangsu Higher Education Institutions and the Natural Science Foundation of Universities in Anhui Province","award":["82171813"],"award-info":[{"award-number":["82171813"]}]},{"name":"the Priority Academic Program Development of Jiangsu Higher Education Institutions and the Natural Science Foundation of Universities in Anhui Province","award":["KJ2021A0835"],"award-info":[{"award-number":["KJ2021A0835"]}]},{"name":"the Priority Academic Program Development of Jiangsu Higher Education Institutions and the Natural Science Foundation of Universities in Anhui Province","award":["BXQN202105"],"award-info":[{"award-number":["BXQN202105"]}]},{"name":"the Natural Science Foundation BoXi Program funded by the First Affiliated Hospital of Soochow University","award":["82171813"],"award-info":[{"award-number":["82171813"]}]},{"name":"the Natural Science Foundation BoXi Program funded by the First Affiliated Hospital of Soochow University","award":["KJ2021A0835"],"award-info":[{"award-number":["KJ2021A0835"]}]},{"name":"the Natural Science Foundation BoXi Program funded by the First Affiliated Hospital of Soochow University","award":["BXQN202105"],"award-info":[{"award-number":["BXQN202105"]}]},{"name":"Priority Academic Program Development of Jiangsu Higher Education Institutions","award":["82171813"],"award-info":[{"award-number":["82171813"]}]},{"name":"Priority Academic Program Development of Jiangsu Higher Education Institutions","award":["KJ2021A0835"],"award-info":[{"award-number":["KJ2021A0835"]}]},{"name":"Priority Academic Program Development of Jiangsu Higher Education Institutions","award":["BXQN202105"],"award-info":[{"award-number":["BXQN202105"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Inflammasomes are cytosolic sensors of pathogens. Their activation can lead to the induction of caspase-1-mediated inflammatory responses and the release of several proinflammatory cytokines, including IL-1\u03b2. There is a complex relationship between viral infection and the nucleotide-binding oligomerization domain-like receptors family pyrin domain-containing 3 (NLRP3) inflammasome. The activation of the NLRP3 inflammasome is essential for antiviral immunity, while excessive NLRP3 inflammasome activation may lead to excessive inflammation and pathological damage. Meanwhile, viruses have evolved strategies to suppress the activation of inflammasome signaling pathways, thus escaping immune responses. In this study, we investigated the inhibitory effect of coxsackievirus B3 (CVB3), a positive single-strand RNA virus, on the activation of the NLRP3 inflammasome in macrophages. CVB3-infected mice had significantly lower production of IL-1\u03b2 and a lower level of NLRP3 in the small intestine after LPS stimulation. Furthermore, we found that CVB3 infection inhibited NLRP3 inflammasome activation and IL-1\u03b2 production in macrophages by suppressing the NF-\u03baB signaling pathway and ROS production. Additionally, CVB3 infection increased the susceptibility of mice to Escherichia coli infection by decreasing IL-1\u03b2 production. Collectively, our study revealed a novel mechanism of NLRP3 inflammasome activation by suppressing the NF-\u03baB pathway and ROS production in LPS-induced macrophages. Our findings may provide new ideas for antiviral treatment and drug development for CVB3 infection.<\/jats:p>","DOI":"10.3390\/v15051078","type":"journal-article","created":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T09:54:53Z","timestamp":1682675693000},"page":"1078","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["CVB3 Inhibits NLRP3 Inflammasome Activation by Suppressing NF-\u03baB Pathway and ROS Production in LPS-Induced Macrophages"],"prefix":"10.3390","volume":"15","author":[{"given":"Yanqi","family":"Wang","sequence":"first","affiliation":[{"name":"Institute of Biology and Medical Sciences, Soochow University, Building 703, 199 Ren-ai Road, Suzhou 215123, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhirong","family":"Sun","sequence":"additional","affiliation":[{"name":"Institute of Biology and Medical Sciences, Soochow University, Building 703, 199 Ren-ai Road, Suzhou 215123, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongkai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Suzhou Center for Disease Prevention and Control, 72 Sanxiang Road, Suzhou 215004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yahui","family":"Song","sequence":"additional","affiliation":[{"name":"Institute of Biology and Medical Sciences, Soochow University, Building 703, 199 Ren-ai Road, Suzhou 215123, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Biology and Medical Sciences, Soochow University, Building 703, 199 Ren-ai Road, Suzhou 215123, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2652-8244","authenticated-orcid":false,"given":"Wei","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Biology and Medical Sciences, Soochow University, Building 703, 199 Ren-ai Road, Suzhou 215123, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9305-9129","authenticated-orcid":false,"given":"Min","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Biology and Medical Sciences, Soochow University, Building 703, 199 Ren-ai Road, Suzhou 215123, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"629","DOI":"10.2217\/fmb.15.5","article-title":"Coxsackievirus B3 replication and pathogenesis","volume":"10","author":"Garmaroudi","year":"2015","journal-title":"Future Microbiol."},{"key":"ref_2","first-page":"1120","article-title":"Adult heart transplant: Indications and outcomes","volume":"6","author":"Alraies","year":"2014","journal-title":"J. Thorac. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.ymeth.2006.07.009","article-title":"Coxsackievirus-induced myocarditis in mice: A model of autoimmune disease for studying immunotoxicity","volume":"41","author":"Fairweather","year":"2007","journal-title":"Methods"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2900","DOI":"10.1128\/JVI.05738-11","article-title":"Sensing of RNA viruses: A review of innate immune receptors involved in recognizing RNA virus invasion","volume":"86","author":"Jensen","year":"2012","journal-title":"J. Virol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"321","DOI":"10.3389\/fmicb.2019.00321","article-title":"Interactions Between Enteroviruses and the Inflammasome: New Insights into Viral Pathogenesis","volume":"10","author":"Xiao","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1146\/annurev-immunol-031210-101405","article-title":"The inflammasome NLRs in immunity, inflammation, and associated diseases","volume":"29","author":"Davis","year":"2011","journal-title":"Annu. Rev. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nri2936","article-title":"Emerging inflammasome effector mechanisms","volume":"11","author":"Lamkanfi","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"H1438","DOI":"10.1152\/ajpheart.00441.2014","article-title":"Involvement of NLRP3 inflammasome in CVB3-induced viral myocarditis","volume":"307","author":"Wang","year":"2014","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"14302","DOI":"10.1038\/srep14302","article-title":"Enterovirus 71 2C Protein Inhibits NF-kappaB Activation by Binding to RelA(p65)","volume":"5","author":"Du","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2887","DOI":"10.1038\/s41598-018-20958-1","article-title":"Pyroptosis induced by enterovirus 71 and coxsackievirus B3 infection affects viral replication and host response","volume":"8","author":"Wang","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.jhep.2016.12.018","article-title":"HBV inhibits LPS-induced NLRP3 inflammasome activation and IL-1beta production via suppressing the NF-kappaB pathway and ROS production","volume":"66","author":"Yu","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5271","DOI":"10.4049\/jimmunol.0903035","article-title":"Signaling through the A2B adenosine receptor dampens endotoxin-induced acute lung injury","volume":"184","author":"Schingnitz","year":"2010","journal-title":"J. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1001\/archsurg.1970.01340280030009","article-title":"Intestinal mucosal lesion in low-flow states. I. A morphological, hemodynamic, and metabolic reappraisal","volume":"101","author":"Chiu","year":"1970","journal-title":"Arch. Surg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.2217\/fmb.12.96","article-title":"Manipulating intestinal immunity and microflora: An alternative solution to viral myocarditis?","volume":"7","author":"Qian","year":"2012","journal-title":"Future Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"217","DOI":"10.3858\/emm.2009.41.4.058","article-title":"p47phox, the phagocyte NADPH oxidase\/NOX2 organizer: Structure, phosphorylation and implication in diseases","volume":"41","author":"Dang","year":"2009","journal-title":"Exp. Mol. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"81","DOI":"10.3389\/fcimb.2018.00081","article-title":"Activation of the NLRP3 Inflammasome Pathway by Uropathogenic Escherichia coli Is Virulence Factor-Dependent and Influences Colonization of Bladder Epithelial Cells","volume":"8","author":"Demirel","year":"2018","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.3346\/jkms.2013.28.10.1415","article-title":"NLRP3 inflammasome and host protection against bacterial infection","volume":"28","author":"Kim","year":"2013","journal-title":"J. Korean Med. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e003870","DOI":"10.1161\/CIRCHEARTFAILURE.117.003870","article-title":"NOD2 (Nucleotide-Binding Oligomerization Domain 2) Is a Major Pathogenic Mediator of Coxsackievirus B3-Induced Myocarditis","volume":"10","author":"Tschope","year":"2017","journal-title":"Circ. Heart Failure"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1096\/fj.201800301RRR","article-title":"NLRP3 deficiency exacerbates enterovirus infection in mice","volume":"33","author":"Wang","year":"2019","journal-title":"FASEB J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.molimm.2019.07.012","article-title":"Macrophage NLRP3 inflammasome activated by CVB3 capsid proteins contributes to the development of viral myocarditis","volume":"114","author":"Bao","year":"2019","journal-title":"Mol. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1038\/nature04515","article-title":"Cryopyrin activates the inflammasome in response to toxins and ATP","volume":"440","author":"Mariathasan","year":"2006","journal-title":"Nature"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/5\/1078\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:25:42Z","timestamp":1760124342000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/5\/1078"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,28]]},"references-count":21,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["v15051078"],"URL":"https:\/\/doi.org\/10.3390\/v15051078","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,28]]}}}