{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T07:02:35Z","timestamp":1780470155173,"version":"3.54.1"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Shandong Provincial Natural Science Foundation","doi-asserted-by":"publisher","award":["2023YFC2506004"],"award-info":[{"award-number":["2023YFC2506004"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Shandong Provincial Natural Science Foundation","doi-asserted-by":"publisher","award":["2025005B"],"award-info":[{"award-number":["2025005B"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Shandong Provincial Natural Science Foundation","doi-asserted-by":"publisher","award":["2023014D"],"award-info":[{"award-number":["2023014D"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Shandong Provincial Natural Science Foundation","doi-asserted-by":"publisher","award":["2022004Q"],"award-info":[{"award-number":["2022004Q"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Shandong Provincial Natural Science Foundation","doi-asserted-by":"publisher","award":["ZR2023LZY003"],"award-info":[{"award-number":["ZR2023LZY003"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Shandong Provincial Natural Science Foundation","doi-asserted-by":"publisher","award":["ZR2023QH494"],"award-info":[{"award-number":["ZR2023QH494"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Shandong Provincial Natural Science Foundation","doi-asserted-by":"publisher","award":["ZR2023QH546"],"award-info":[{"award-number":["ZR2023QH546"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Shandong Provincial Natural Science Foundation","doi-asserted-by":"publisher","award":["SYS202202"],"award-info":[{"award-number":["SYS202202"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The gut microbiota plays a critical role in shaping host antiviral immunity, particularly through the regulation of type I interferon (IFN-I) signaling. Infants are highly vulnerable to viral infections, largely due to their adaptive immune immaturity. Identifying specific commensal bacteria capable of enhancing IFN-I responses represents a promising strategy to boost antiviral defense in this vulnerable population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Forty-five bacterial strains were isolated from fecal samples of infants aged 0-3 years. Their ability to modulate virus-induced IFN-I expression was evaluated using qPCR-based assays in cell lines infected with Sendai virus (SeV). One strain,\n                      <jats:italic>Escherichia coli JNL-EC1<\/jats:italic>\n                      , was selected for further genomic analysis, virulence gene profiling, and hemolysis testing. We assessed IFN-I and ISGs expression, as well as the phosphorylation of STING, TBK1, and IRF3, under conditions of cGAS-STING activation, TBK1 or IRF3-5D overexpression, and HSV-1 or SeV infection. The active components of its metabolites were fractionated using ethanol and chloroform extraction. Antiviral effects were evaluated in HEK293T, INT407, and THP-1 cells, as well as in a SeV-infected mouse model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among the 45 isolates, metabolites of\n                      <jats:italic>E. coli JNL-EC1<\/jats:italic>\n                      significantly enhanced SeV- and HSV-1(herpes simplex virus 1)-induced IFN-I signaling activation. Genomic analysis confirmed that\n                      <jats:italic>E. coli JNL-EC1<\/jats:italic>\n                      resembles a commensal strain, lacking typical pathogenic determinants and exhibiting a non-hemolytic phenotype. The metabolites potentiated cGAS\/STING- and TBK1-mediated IFN-I signaling but did not further enhance IRF3-5D-induced gene expression. Moreover, the metabolites increased the phosphorylation of STING, TBK1, and IRF3 following HSV-1 or SeV infection. Active components were present in both water-soluble (0-60% ethanol) and chloroform-extracted fractions and were heat-stable, suggesting the involvement of multiple non-proteinaceous metabolites. Functionally, metabolite pretreatment reduced the replication of GFP-tagged HSV-1 and vesicular stomatitis virus (VSV) in vitro.\n                      <jats:italic>E. coli JNL-EC1<\/jats:italic>\n                      significantly upregulated Ifnb1 expression in the spleen and modulated both the composition and activation status of immune cell populations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      These findings identify\n                      <jats:italic>E. coli JNL-EC1<\/jats:italic>\n                      as a gut commensal with broad antiviral-enhancing properties and reveal a microbiota-mediated mechanism that primes antiviral immunity through the IFN-I pathway.\n                    <\/jats:p>\n                  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China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Linyi People\u2019s Hospital, Shandong Second Medical University","place":["Linyi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cunfei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Linyi People's Hospital, Shandong Second Medical University","place":["Linyi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changzhong","family":"Jin","sequence":"additional","affiliation":[{"name":"Jinan Microecological Biomedicine Shandong Laboratory","place":["Jinan, China"]},{"name":"State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang 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