RIPK3 Restricts Viral Pathogenesis via Cell Death-Independent Neuroinflammation.

ABSTRACT: Receptor-interacting protein kinase-3 (RIPK3) is an activator of necroptotic cell death, but recent work has implicated additional roles for RIPK3 in inflammatory signaling independent of cell death. However, while necroptosis has been shown to contribute to antiviral immunity, death-independent roles for RIPK3 in host defense have not been demonstrated. Using a mouse model of West Nile virus (WNV) encephalitis, we show that RIPK3 restricts WNV pathogenesis independently of cell death. Ripk3^-/- mice exhibited enhanced mortality compared to wild-type (WT) controls, while mice lacking the necroptotic effector MLKL, or both MLKL and caspase-8, were unaffected. The enhanced susceptibility of Ripk3^-/- mice arose from suppressed neuronal chemokine expression and decreased c

SUBMITTER: Daniels BP 

PROVIDER: S-EPMC5405738 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature