Activation and inhibition of JAK-STAT signal transduction by RNA viruses

The investigation of interferon (IFN)-stimulated signal transduction leading to antiviral gene expression revealed the first members of the JAK and STAT protein families. The importance of IFN signaling in the innate cellular response to virus infection is highlighted by the evolution of numerous virus-encoded IFN evasion strategies that can prevent IFN production or antagonize downstream responses. Some RNA viruses in the family Paramyxoviridae have evolved the ability to target STAT proteins directly to eliminate antiviral signaling, preventing IFN-stimulated gene expression and innate antiviral responses. The virus-encoded STAT inhibitors are highly homologous to each other, and target STATs through protein interactions. However, in-depth investigations of the biochemical and cellular mechanisms have revealed that individual paramyxovirus genera have evolved distinct mechanisms to mediate STAT destruction.