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Abstract
STAT2 is unique among the STAT family of transcription factors in that its activation is driven predominantly by only two classes of cell surface receptors: Type I and III interferon receptors. As such, STAT2 plays a critical role in host defenses against viral infections. Viruses have evolved to target STAT2 by either inhibiting its expression, blocking its activity, or by targeting it for degradation. Consequently, these viral onslaughts have driven remarkable divergence in the STAT2 gene across species that is not observed in other STAT family members. Thus, the evolution of STAT2 may preserve its activity and protect each species in the face of an ever-changing viral community.
Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed.
Acknowledgments
The authors would like to thank Sarah Gonzales for helpful discussions and for critically reading the manuscript. This work was supported by the National Institutes of Health (Bethesda, MD): F.C.Z. supported by AI005284 and AI56222 awarded to J.D.F.