Outcomes of RIP Kinase Signaling During Neuroinvasive Viral Infection

Neuroinvasive viral diseases are a considerable and growing burden on global public health. Despite this, these infections remain poorly understood, and the molecular mechanisms that govern protective versus pathological neuroinflammatory responses to infection are a matter of intense investigation. Recent evidence suggests that necroptosis, an immunogenic form of programmed cell death, may contribute to the pathogenesis of viral encephalitis. However, the receptor-interacting protein (RIP) kinases that coordinate necroptosis, RIPK1 and RIPK3, also appear to have unexpected, cell death-independent functions in the central nervous system (CNS) that promote beneficial neuroinflammation during neuroinvasive infection. Here, we review the emerging evidence in this field, with additional discussion of recent work examining roles for RIPK signaling and necroptosis during noninfectious pathologies of the CNS, as these studies provide important additional insight into the potential for specialized neuroimmune functions for the RIP kinases.