RIPK3 interacts with MAVS to regulate type I IFN-mediated immunity to Influenza A virus infection

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 (mφ) to produce type i ifn in the lungs of infected mice. in mφ 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-β mrna stability. collectively,our findings indicate a novel role for ripk3 in regulating mφ-mediated type i ifn anti-viral immunity,independent of its conventional role in necroptosis. © 2017 downey et al.