Rotavirus VP3 targets MAVS for degradation to inhibit type III interferon expression in intestinal epithelial cells

Siyuan Ding, Shu Zhu, Lili Ren, Ningguo Feng, Yanhua Song, Xiaomei Ge, Bin Li, Richard A. Flavell, Harry B. Greenberg

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Rotaviruses (RVs), a leading cause of severe diarrhea in young children and many mammalian species, have evolved multiple strategies to counteract the host innate immunity, specifically interferon (IFN) signaling through RV non-structural protein 1 (NSP1). However, whether RV structural components also subvert antiviral response remains under-studied. Here, we found that MAVS, critical for the host RNA sensing pathway upstream of IFN induction, is degraded by the RV RNA methyl-and guanylyl-transferase (VP3) in a host-range-restricted manner. Mechanistically, VP3 localizes to the mitochondria and mediates the phosphorylation of a previously unidentified SPLTSS motif within the MAVS proline-rich region, leading to its proteasomal degradation and blockade of IFN-l production in RV-infected intestinal epithelial cells. Importantly, VP3 inhibition of MAVS activity contributes to enhanced RV replication and to viral pathogenesis in vivo. Collectively, our findings establish RV VP3 as a viral antagonist of MAVS function in mammals and uncover a novel pathogen-mediated inhibitory mechanism of MAVS signaling. DOI: https://doi.org/10.7554/eLife.39494.001.

Original languageEnglish
Article numbere39494.
JournaleLife
Volume7
DOIs
StatePublished - Nov 1 2018
Externally publishedYes

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    Ding, S., Zhu, S., Ren, L., Feng, N., Song, Y., Ge, X., Li, B., Flavell, R. A., & Greenberg, H. B. (2018). Rotavirus VP3 targets MAVS for degradation to inhibit type III interferon expression in intestinal epithelial cells. eLife, 7, [e39494.]. https://doi.org/10.7554/eLife.39494