| First Author | Downey J | Year | 2017 |
| Journal | PLoS Pathog | Volume | 13 |
| Issue | 4 | Pages | e1006326 |
| PubMed ID | 28410401 | Mgi Jnum | J:246918 |
| Mgi Id | MGI:5915166 | Doi | 10.1371/journal.ppat.1006326 |
| Citation | Downey J, et al. (2017) RIPK3 interacts with MAVS to regulate type I IFN-mediated immunity to Influenza A virus infection. PLoS Pathog 13(4):e1006326 |
| abstractText | The type I interferon pathway plays a critical role in both host defense and tolerance against viral infection and thus requires refined regulatory mechanisms. RIPK3-mediated necroptosis has been shown to be involved in anti-viral immunity. However, the exact role of RIPK3 in immunity to Influenza A Virus (IAV) is poorly understood. In line with others, we, herein, show that Ripk3-/- mice are highly susceptible to IAV infection, exhibiting elevated pulmonary viral load and heightened morbidity and mortality. Unexpectedly, this susceptibility was linked to an inability of RIKP3-deficient macrophages (Mphi) to produce type I IFN in the lungs of infected mice. In Mphi infected with IAV in vitro, we found that RIPK3 regulates type I IFN both transcriptionally, by interacting with MAVS and limiting RIPK1 interaction with MAVS, and post-transcriptionally, by activating protein kinase R (PKR)-a critical regulator of IFN-beta mRNA stability. Collectively, our findings indicate a novel role for RIPK3 in regulating Mphi-mediated type I IFN anti-viral immunity, independent of its conventional role in necroptosis. |
