Characterization of RHIM Domain Functionality in Viral Pathogens Through Interaction with Necroptotic Machinery

Abstract

Necroptotic cell death occurs following cellular stress conditions in which there is a potential benefit to the host to encouraging an inflammatory response. Often, this is an additional defense against pathogens, although the exact mechanism of activation is often unclear. This signaling cascade, unlike apoptotic cell death, does not involve the activation of caspases and is dependent on the kinase activity and interaction of RIP homotypic interaction motifs (RHIM) contained within several proteins within the cascade. However, non-mammalian RHIM domains have been observed with a range of potential positive and negative effects on the cell. Through a novel RHIM-swap screen, we evaluated the cellular localization of these proposed RHIMs as a predictive measure of binding ability. These predictions were corroborated through protein interaction experiments. The results of these experiments suggest a role in RHIM binding in some coronavirus infections and may indicate a novel approach to understanding inflammatory responses to some viral infections.