| First Author | Ding S | Year | 2018 |
| Journal | Elife | Volume | 7 |
| PubMed ID | 30460894 | Mgi Jnum | J:326730 |
| Mgi Id | MGI:6881294 | Doi | 10.7554/eLife.39494 |
| Citation | Ding S, et al. (2018) Rotavirus VP3 targets MAVS for degradation to inhibit type III interferon expression in intestinal epithelial cells. Elife 7:e39494 |
| abstractText | 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-lambda 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. |
