{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T08:04:03Z","timestamp":1790755443533,"version":"4.1.0"},"reference-count":48,"publisher":"Microbiology Society","issue":"10","license":[{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,1]]},"abstract":"<jats:p>Viperin has antiviral function against many viruses, including dengue virus (DENV), when studied in cells in culture. Here, the antiviral actions of viperin were defined both <jats:italic>in vitro<\/jats:italic> and in a mouse <jats:italic>in vivo<\/jats:italic> model of DENV infection. Murine embryonic fibroblasts (MEFs) derived from mice lacking viperin (vip<jats:sup>\u2212\/\u2212<\/jats:sup>) showed enhanced DENV infection, accompanied by increased IFN-\u03b2 and induction of ISGs; IFIT1 and CXCL-10 but not IRF7, when compared to wild-type (WT) MEFs. In contrast, subcutaneous challenge of immunocompetent WT and vip<jats:sup>\u2212\/\u2212<\/jats:sup> mice with DENV did not result in enhanced infection. Intracranial infection with DENV resulted in body weight loss and neurological disease with a moderate increase in mortality in vip<jats:sup>\u2212\/\u2212<\/jats:sup> compared with WT mice, although this was not accompanied by altered brain morphology, immune cell infiltration or DENV RNA level in the brain. Similarly, DENV induction of IFN-\u03b2, IFIT1, CXCL-10, IRF7 and TNF-\u03b1 was not significantly different in WT and vip<jats:sup>\u2212\/\u2212<\/jats:sup> mouse brain, although there was a modest but significant increase in DENV induction of IL-6 and IfI27la in the absence of viperin. NanoString nCounter analysis confirmed no significant difference in induction of a panel of inflammatory genes in WT compared to vip<jats:sup>\u2212\/\u2212<\/jats:sup> DENV-infected mouse brains. Further, polyI:C stimulation of bone marrow-derived macrophages (BMDMs) induced TNF-\u03b1, IFN-\u03b2, IL-6 and Nos-2, but responses were not different in BMDMs generated from WT or vip<jats:sup>\u2212\/\u2212<\/jats:sup> mice. Thus, while there is significant evidence of anti-DENV actions of viperin in some cell types <jats:italic>in vitro<\/jats:italic>, for DENV infection <jats:italic>in vivo<\/jats:italic> a lack of viperin does not affect systemic or brain susceptibility to DENV or induction of innate and inflammatory responses.<\/jats:p>","DOI":"10.1099\/jgv.0.001669","type":"journal-article","created":{"date-parts":[[2021,10,19]],"date-time":"2021-10-19T16:35:28Z","timestamp":1634661328000},"source":"Crossref","is-referenced-by-count":10,"title":["Viperin is anti-viral in vitro but is dispensable for restricting dengue virus replication or induction of innate and inflammatory responses in vivo"],"prefix":"10.1099","volume":"102","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7423-5692","authenticated-orcid":false,"given":"Wisam-Hamzah","family":"Al Shujairi","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Pharmacy, University of Babylon, 51001 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