Silencing STATs: lessons from paramyxovirus interferon evasion.

The signal transducer and activator of transcription (STAT) family proteins are essential mediators of cytokine and growth factor functions. The interferon (IFN) family of cytokines is well known as modulators of both innate and adaptive anti-microbial immunity. In response to the evolutionary struggle between host and pathogen, many viruses have developed strategies to bypass the IFN antiviral system. Uniquely, the paramyxoviruses have developed the ability to efficiently inactivate STAT protein function, in many cases using a single virus-encoded protein called 'V'. The V protein plays a central role in STAT inhibition, but mechanistic studies have revealed great diversity in V-dependent STAT signaling evasion among paramyxovirus species. These examples of IFN evasion by STAT protein inactivation can help define targets for antiviral drug design or improving vaccine regimens. Moreover, understanding these STAT inhibition mechanisms are likely to reveal strategic options for the design of STAT-directed therapeutics for treatment of diseases characterized by cytokine hyperactivity.