Rotavirus Degrades Multiple Interferon (IFN) Type Receptors To Inhibit IFN Signaling and Protects against Mortality from Endotoxin in Suckling Mice

Journal of Virology
Adrish SenHarry B Greenberg

Abstract

STAT1 phosphorylation in response to exogenous interferon (IFN) administration can be inhibited by rotaviral replication both in vitro and in vivo In addition many rotavirus strains are resistant to the actions of different IFN types. The regulation by rotaviruses (RVs) of antiviral pathways mediated by multiple IFN types is not well understood. In this study, we find that during infection in vitro and in vivo, RVs significantly deplete IFN type I, II, and III receptors (IFNRs). Regulation of IFNRs occurred exclusively within RV-infected cells and could be abrogated by inhibiting the lysosomal-endosomal degradation pathway. In vitro, IFNR degradation was conserved across multiple RV strains that differ in their modes of regulating IFN induction. In suckling mice, exogenously administered type I, II, or III IFN induced phosphorylation of STAT1-Y701 within intestinal epithelial cells (IECs) of suckling mice. Murine EW strain RV infection transiently activated intestinal STAT1 at 1 day postinfection (dpi) but not subsequently at 2 to 3 dpi. In response to injection of purified IFN-α/β or -λ, IECs in EW-infected mice exhibited impaired STAT1-Y701 phosphorylation, correlating with depletion of different intestinal IFNRs and impaired...Continue Reading

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Citations

Jan 25, 2018·Viruses·Harshad IngleMegan T Baldridge
Mar 25, 2019·International Journal of Molecular Sciences·Megan L StaniferSteeve Boulant
Jun 15, 2019·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Kalliopi PervolarakiMegan L Stanifer
Oct 28, 2019·Nature Microbiology·Tingting GuoHui Zheng
Aug 7, 2019·Vaccines·Mehdi R M BidokhtiClaudia Baule

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