{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:29:01Z","timestamp":1787059741721,"version":"build-2736575974"},"reference-count":63,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI153195"],"award-info":[{"award-number":["R01AI153195"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2026,8,18]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Beyond a physical barrier, the lung epithelium provides an essential line of defense against infectious pathogens, such as influenza A viruses (IAVs), by producing antimicrobial factors and triggering innate and adaptive immunity. On the other hand, IAV infects lung epithelial cells and manipulates their function to establish a non-protective, permissive environment. Identification of epithelial factors and pathways that can be targeted to restore optimal immunity would provide new therapeutic options against IAV. Here, we demonstrate an unexpected non-immune function for the cytokine RELM\u0251 in mediating a permissive environment for IAV infection through lung epithelial cell-intrinsic effects. Murine infection with IAV A\/California\/04\/2009 (H1N1) led to significant RELM\u0251 secretion by IAV-infected EpCAM+ epithelial cells. Both whole-body and club cell-specific RELM\u0251-deficient mice (\n                      <jats:italic toggle=\"yes\">Retnla<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      and\n                      <jats:italic toggle=\"yes\">Retnla<\/jats:italic>\n                      <jats:sup>\u0394CC10<\/jats:sup>\n                      ) had significantly reduced infectious virus, specifically in epithelial cells, whereas the lung immune response was unaffected. RELM\u0251 treatment increased IAV infection of murine lung epithelial cell lines, and transcriptomic analysis indicated that RELM\u0251-induced permissiveness to IAV was associated with cell-intrinsic changes in metabolic activity. Collectively, these studies suggest a direct non-immune role for RELM\u0251 in mediating a virus-permissive environment in epithelial cells.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>Seasonal influenza causes over 3 million cases of severe disease and an estimated 500,000 deaths worldwide annually, highlighting the need for new therapeutic targets. The host response to infection is a significant factor in determining influenza outcome and can be subverted by the virus. The epithelial barrier is the first line of defense and a target for influenza A viruses (IAVs), which seek to establish a permissive environment for their own growth, and these pathways could be targeted to control viral burden. Here, we identify RELM\u0251, a new host factor that is induced in epithelial cells upon IAV infection and aids viral infection. Through RELM\u0251-deficient mouse models, lung epithelial cell cultures, and gene expression analysis, we show that RELM\u0251 acts directly on epithelial cells to change cell metabolic pathways and promote viral growth. These findings provide a unique epithelial cell protein that can be inhibited to limit influenza infection.<\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.02225-25","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T13:01:54Z","timestamp":1784206914000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["RELM\u03b1 establishes a permissive environment for influenza virus infection through direct effects on lung epithelial cells"],"prefix":"10.1128","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3112-7827","authenticated-orcid":false,"given":"Roksana","family":"Shirazi","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03nawhv43","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Plant Pathology, University of California, Riverside","place":["Riverside, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Yong","family":"Kim","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03nawhv43","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Biomedical Sciences, School of Medicine, University of California, Riverside","place":["Riverside, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1161-7586","authenticated-orcid":false,"given":"Aaron","family":"Cruz","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03nawhv43","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Plant Pathology, University of California, Riverside","place":["Riverside, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James P.","family":"Stumpff","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03nawhv43","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Plant Pathology, University of California, Riverside","place":["Riverside, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6448-9827","authenticated-orcid":false,"given":"Stefanie N.","family":"Sveiven","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03nawhv43","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Biomedical Sciences, School of Medicine, University of California, Riverside","place":["Riverside, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6079-3477","authenticated-orcid":false,"given":"Sumaya","family":"Alaama","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03nawhv43","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Biomedical Sciences, School of Medicine, University of California, Riverside","place":["Riverside, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennell","family":"Jennett","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03nawhv43","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Biomedical Sciences, School of Medicine, University of California, Riverside","place":["Riverside, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8651-2186","authenticated-orcid":false,"given":"Brandon H.","family":"Le","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03nawhv43","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute for Integrative Genome Biology, Bioinformatics Core Facility, Department of Botany and Plant Sciences, University of California, Riverside","place":["Riverside, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1807-5161","authenticated-orcid":true,"given":"Meera G.","family":"Nair","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03nawhv43","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Biomedical Sciences, School of Medicine, University of California, Riverside","place":["Riverside, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7387-6351","authenticated-orcid":false,"given":"Juliet","family":"Morrison","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03nawhv43","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Plant Pathology, University of California, Riverside","place":["Riverside, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","unstructured":"WHO. 2023. 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