ID: 115. Issue 1 (November 2015)

• Record Type: Journal Article
• Authors: Lin, Jian-Da; Feng, Ningguo; Sen, Adrish; Balan, Murugabaskar; Tseng, Hsiang-Chi; McElrath, Constance; Durbin, Russell K.; Greenberg, Harry B.; Durbin, Joan E.; Kotenko, Sergei V.
• Is Part Of: Cytokine. Volume 76:Issue 1(2015)
• Page Start: 87
• Publication Date: 2015-11
• Subjects: Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2015.08.142
• Languages: English
• ISSNs: 1043-4666

Abstract

<abstract xml:lang="en" abstract-type="author" id="ab005"> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <p id="sp005">Types I and III IFNs exert common antiviral activities through distinct receptors, and their relative importance for antiviral protection of different organ remains to be fully explored. Mouse strains deficient in type-specific IFN signaling were used to dissect distinct and overlapping contributions of type I and III IFNs to protection against homologous murine (EW-strain) and heterologous simian (RRV-strain) rotavirus infection of the intestine. EW-RV replicated to similar levels in IFN-<italic>λ</italic>R, IFN-<italic>α</italic>R, IFN-<italic>α</italic>/<italic>λ</italic>R, IFN-<italic>α</italic>/<italic>γ</italic>R and STAT1 deficient suckling mice between 2–7 days post-infection (dpi); and only a moderate increase in fecal shedding was observed in IFN-<italic>λ</italic>R and STAT1 knock-out (KO) mice at 8–9 dpi. In contrast, Rag2 KO mice showed chronic viral shedding, demonstrating that the homologous EW-RV efficiently antagonizes murine IFN responses, with viral clearance dependent upon adaptive immune responses. Unlike EW-RV, replication of the heterologous RRV was significantly increased in gastro-intestinal tract of either IFN-<italic>λ</italic>R or IFN-<italic>α</italic>R deficient mice, and was further enhanced in doubly deficient IFN-<italic>α</italic>/<italic>λ</italic>R KO animals, demonstrating the sensitivity of RRV to IFN-mediated antiviral protection, and revealing important, and cooperative roles for both type I and type III IFNs in limiting RRV replication. Similarly, both type I and III IFNs helped to limit extra-intestinal RRV spread, whereas type I IFNs were essential for controlling RRV replication in mesenteric lymph nodes. Overall, these results demonstrate a murine host-specific inhibition of IFN's antiviral activity by EW-RV, but cooperative action by type I and type III IFNs in limiting simian RRV growth and spread in mice.</p> </sec> </abstract>