{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T22:50:19Z","timestamp":1792018219716,"version":"4.4.0"},"reference-count":48,"publisher":"American Society for Microbiology","issue":"20","license":[{"start":{"date-parts":[[2016,10,15]],"date-time":"2016-10-15T00:00:00Z","timestamp":1476489600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2016,10,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Type I interferons (IFNs) crucially contribute to host survival upon viral infections. Robust expression of type I IFNs (IFN-\u03b1\/\u03b2) and induction of an antiviral state critically depend on amplification of the IFN signal via the type I IFN receptor (IFNAR). A small amount of type I IFN produced early upon virus infection binds the IFNAR and activates a self-enhancing positive feedback loop, resulting in induction of large, protective amounts of IFN-\u03b1. Unexpectedly, we found robust, systemic IFN-\u03b1 expression upon infection of IFNAR knockout mice with the orthomyxovirus Thogoto virus (THOV). The IFNAR-independent IFN-\u03b1 production required\n            <jats:italic>in vivo<\/jats:italic>\n            conditions and was not achieved during\n            <jats:italic>in vitro<\/jats:italic>\n            infection. Using replication-incompetent THOV-derived virus-like particles, we demonstrate that IFNAR-independent type I IFN induction depends on viral polymerase activity but is largely independent of viral replication. To discover the cell type responsible for this effect, we used type I IFN reporter mice and identified CD11b\n            <jats:sup>+<\/jats:sup>\n            F4\/80\n            <jats:sup>+<\/jats:sup>\n            myeloid cells within the peritoneal cavity of infected animals as the main source of IFNAR-independent type I IFN, corresponding to the particular tropism of THOV for this cell type.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Type I IFNs are crucial for the survival of a host upon most viral infections, and, moreover, they shape subsequent adaptive immune responses. Production of protective amounts of type I IFN critically depends on the positive feedback amplification via the IFNAR. Unexpectedly, we observed robust IFNAR-independent type I IFN expression upon THOV infection and unraveled molecular mechanisms and determined the tissue and cell type involved. Our data indicate that the host can effectively use alternative pathways to induce type I IFN responses if the classical feedback amplification is not available. Understanding how type I IFN can be produced in large amounts independently of IFNAR-dependent enhancement will identify mechanisms which might contribute to novel therapeutic strategies to fight viral pathogens.\n          <\/jats:p>","DOI":"10.1128\/jvi.00744-16","type":"journal-article","created":{"date-parts":[[2016,8,11]],"date-time":"2016-08-11T02:48:46Z","timestamp":1470883726000},"page":"9330-9337","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":9,"title":["<i>In Vivo<\/i>\n            Conditions Enable IFNAR-Independent Type I Interferon Production by Peritoneal CD11b\n            <sup>+<\/sup>\n            Cells upon Thogoto Virus Infection"],"prefix":"10.1128","volume":"90","author":[{"given":"Georg","family":"Kochs","sequence":"first","affiliation":[{"name":"Institute of Virology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Anzaghe","sequence":"additional","affiliation":[{"name":"Junior Research Group, Novel Vaccination Strategies and Early Immune Responses, Paul-Ehrlich-Institut, Langen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Kronhart","sequence":"additional","affiliation":[{"name":"Junior Research Group, Novel Vaccination Strategies and Early Immune Responses, Paul-Ehrlich-Institut, Langen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Wagner","sequence":"additional","affiliation":[{"name":"Institute of Virology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Gogesch","sequence":"additional","affiliation":[{"name":"Junior Research Group, Novel Vaccination Strategies and Early Immune Responses, 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