{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T06:32:48Z","timestamp":1789453968124,"version":"build-2803163510"},"reference-count":56,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"37","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2023,9,15]]},"abstract":"<jats:p>Norovirus is a leading cause of epidemic viral gastroenteritis, with no currently approved vaccines or antivirals. Murine norovirus (MNoV) is a well-characterized model of norovirus pathogenesis in vivo, and persistent strains exhibit lifelong intestinal infection. Interferon-\u03bb (IFN-\u03bb) is a potent antiviral that rapidly cures MNoV. We previously demonstrated that IFN-\u03bb signaling in intestinal epithelial cells (IECs) controls persistent MNoV, and here demonstrate that IFN-\u03bb acts on tuft cells, the exclusive site of MNoV persistence, to limit infection. While interrogating the source of IFN-\u03bb to regulate MNoV, we confirmed that MDA5-MAVS signaling, required for IFN-\u03bb induction to MNoV in vitro, controls persistent MNoV in vivo. We demonstrate that MAVS in IECs and not immune cells controls MNoV. MAVS in nonsusceptible enterocytes, but not in tuft cells, restricts MNoV, implicating noninfected cells as the IFN-\u03bb source. Our findings indicate that host sensing of MNoV is distinct from cellular tropism, suggesting intercellular communication between IECs for antiviral signaling induction in uninfected bystander cells.<\/jats:p>","DOI":"10.1126\/sciadv.adi2562","type":"journal-article","created":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T17:58:50Z","timestamp":1694627930000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":29,"title":["IFN-\u03bb derived from nonsusceptible enterocytes acts on tuft cells to limit persistent norovirus"],"prefix":"10.1126","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5439-8013","authenticated-orcid":true,"given":"Harshad","family":"Ingle","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Edison Family Center for Genome Sciences &amp; Systems Biology, Washington University School of Medicine, St.\u00a0Louis, MO, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4301-1928","authenticated-orcid":true,"given":"Heyde","family":"Makimaa","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Edison Family Center for Genome Sciences &amp; 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