Surgical Strikes on Host Defenses: Role of the Viral Protease Activity in Innate Immune Antagonism

As a frontline defense mechanism against viral infections, the innate immune system is the primary target of viral antagonism. A number of virulence factors encoded by viruses play roles in circumventing host defenses and augmenting viral replication. Among these factors are viral proteases, which are primarily responsible for maturation of viral proteins, but in addition cause proteolytic cleavage of cellular proteins involved in innate immune signaling. The study of these viral protease-mediated host cleavages has illuminated the intricacies of innate immune networks and yielded valuable insights into viral pathogenesis. In this review, we will provide a brief summary of how proteases of positive-strand RNA viruses, mainly from the Picornaviridae, Flaviviridae and Coronaviridae families, proteolytically process innate immune components and blunt their functions.