Rotavirus NSP1 inhibits NFkappaB activation by inducing proteasome-dependent degradation of beta-TrCP: a novel mechanism of IFN antagonism.

ABSTRACT: Mechanisms by which viruses counter innate host defense responses generally involve inhibition of one or more components of the interferon (IFN) system. Multiple steps in the induction and amplification of IFN signaling are targeted for inhibition by viral proteins, and many of the IFN antagonists have direct or indirect effects on activation of latent cytoplasmic transcription factors. Rotavirus nonstructural protein NSP1 blocks transcription of type I IFNalpha/beta by inducing proteasome-dependent degradation of IFN-regulatory factors 3 (IRF3), IRF5, and IRF7. In this study, we show that rotavirus NSP1 also inhibits activation of NFkappaB and does so by a novel mechanism. Proteasome-mediated degradation of inhibitor of kappaB (IkappaBalpha) is required for NFkappaB activation. Phosphoryl

SUBMITTER: Graff JW 

PROVIDER: S-EPMC2627925 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature