Mechanisms of Interferon Antagonism by Poxviruses

The interferons (IFNs), a group of cytokines that induce the innate immune response and stimulate the adaptive immune response, pose a formidable barrier for viral replication in the host. In response, many viruses have evolved strategies to inhibit the induction and action of IFNs. Poxviruses, with a large genome and an entirely cytoplasmic life cycle, are particularly adept at evading IFNs. Almost every aspect of the IFN system is subject to modulation by specific poxvirus proteins. In recent years, great progress has been made in deciphering the molecular basis for IFN modulation by poxviruses. In particular, a number of poxvirus proteins have been identified to inhibit the signaling pathway that induces IFNs, and the structures of an increasing number of poxvirus IFN modulators have been determined. Here we review the multiple strategies used by poxviruses to modulate the induction, signaling and effectors of IFNs, with an emphasis on the molecular mechanisms of action of the poxvirus proteins.