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• W2036710222 endingPage "e1003478" @default.
• W2036710222 startingPage "e1003478" @default.
• W2036710222 abstract "The type I interferons (IFN-Is) are critical not only in early viral control but also in prolonged T-cell immune responses. However, chronic viral infections such as those of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) in humans and lymphocytic choriomeningitis virus (LCMV) in mice overcome this early IFN-I barrier and induce viral persistence and exhaustion of T-cell function. Although various T-cell-intrinsic and -extrinsic factors are known to contribute to induction of chronic conditions, the roles of IFN-I negative regulators in chronic viral infections have been largely unexplored. Herein, we explored whether 2′–5′ oligoadenylate synthetase-like 1 (OASL1), a recently defined IFN-I negative regulator, plays a key role in the virus-specific T-cell response and viral defense against chronic LCMV. To this end, we infected Oasl1 knockout and wild-type mice with LCMV CL-13 (a chronic virus) and monitored T-cell responses, serum cytokine levels, and viral titers. LCMV CL-13-infected Oasl1 KO mice displayed a sustained level of serum IFN-I, which was primarily produced by splenic plasmacytoid dendritic cells, during the very early phase of infection (2–3 days post-infection). Oasl1 deficiency also led to the accelerated elimination of viremia and induction of a functional antiviral CD8 T-cell response, which critically depended on IFN-I receptor signaling. Together, these results demonstrate that OASL1-mediated negative regulation of IFN-I production at an early phase of infection permits viral persistence and suppresses T-cell function, suggesting that IFN-I negative regulators, including OASL1, could be exciting new targets for preventing chronic viral infection." @default.
• W2036710222 created "2016-06-24" @default.
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• W2036710222 creator A5077721033 @default.
• W2036710222 creator A5084556406 @default.
• W2036710222 date "2013-07-18" @default.
• W2036710222 modified "2023-10-16" @default.
• W2036710222 title "Negative Regulation of Type I IFN Expression by OASL1 Permits Chronic Viral Infection and CD8+ T-Cell Exhaustion" @default.
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• W2036710222 doi "https://doi.org/10.1371/journal.ppat.1003478" @default.
• W2036710222 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3715418" @default.
• W2036710222 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23874199" @default.
• W2036710222 hasPublicationYear "2013" @default.
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