Rotavirus degrades interferon receptors and protects against mortality from endotoxin

What is it about?

Antiviral functions of types 1, 2, and 3 IFN are mediated by receptor-dependent activation of STAT1. Here we find that RV degrades the types 1, 2, and 3 IFN receptors (IFNR) in vitro. In a suckling mouse model, RV effectively blocked STAT1 activation and transcription following injection of different purified IFNs. This correlated with significantly decreased protein expression of intestinal types 1 and 2 IFNRs. Recent studies demonstrate that in mice, LPS-induced lethality is prevented by genetic ablation of IFN signaling genes such as IFNAR1 and STAT1. When suckling mice were infected with RV they were substantially protected from lethal exposure to endotoxin. These findings provide novel insights into the mechanisms underlying rotavirus regulation of different interferons and are likely to stimulate new research into both rotavirus pathogenesis and endotoxemia.

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Why is it important?

Rotavirus (RV) displays a remarkable degree of insensitivity to the actions of different interferon (IFN) types, and blocks antiviral signaling from interferon receptors (IFNRs). Sen et al show that RVs mediate the depletion of types I, II, and III IFNRs by orchestrating their lysosomal degradation. Decreased expression of different IFNRs, and inhibition of IFN-mediated antiviral signaling, also occurs in vivo after RV infection. Such pleiotropic subversion of IFN signaling by RV may be beneficial in certain contexts. Here, it is shown that RV significantly protects suckling mice from lethal endotoxin exposure, an outcome dependent on functional IFN responses.