The dynamic interface of viruses with STATs.

Harrison, Angela R; Moseley, Gregory W

Viruses commonly antagonise the antiviral type I interferon response by targeting signal transducers and activators of transcription (STAT) 1 and 2, key mediators of interferon signalling. Other STAT family members mediate signalling by diverse cytokines important to infection, but their relationship with viruses is more complex. Importantly, virus-STAT interaction can be antagonistic or stimulatory depending on diverse viral and cellular factors. While STAT antagonism can suppress immune pathways, many viruses promote activation of specific STATs to support viral gene expression and/or produce cellular conditions conducive to infection. It is also becoming increasingly clear that viruses can hijack non-canonical STAT functions to benefit infection. For a number of viruses, STAT function is dynamically modulated through infection as requirements for replication change. Given the critical role for STATs in infection by diverse viruses, the virus:STAT interface is an attractive target for the development of antivirals and live-attenuated viral vaccines. Here, we review current understanding of the complex and dynamic virus:STAT interface, and discuss how this relationship might be harnessed for medical applications.