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Structural Elucidation of Viral Antagonism of Innate Immunity at the STAT1 Interface

Abstract : To evade immunity, many viruses express interferon antagonists that target STAT transcription factors as a major component of pathogenesis. Because of a lack of direct structural data, these interfaces are poorly understood. We report the structural analysis of full-length STAT1 binding to an interferon antagonist of a human pathogenic virus. The interface revealed by transferred cross-saturation NMR is complex, involving multiple regions in both the viral and cellular proteins. Molecular mapping analysis, combined with biophysical characterization and in vitro/in vivo functional assays, indicates that the interface is significant in disease caused by a pathogenic field-strain lyssavirus, with critical roles for contacts between the STAT1 coiled-coil/DNA-binding domains and specific regions within the viral protein. These data elucidate the potentially complex nature of IFN antagonist/STAT interactions, and the spatial relationship of protein interfaces that mediate immune evasion and replication, providing insight into how viruses can regulate these essential functions via single multifunctional proteins.
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Submitted on : Monday, June 15, 2020 - 4:25:37 PM
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Md Alamgir Hossain, Florence Larrous, Stephen Rawlinson, Jingyu Zhan, Ashish Sethi, et al.. Structural Elucidation of Viral Antagonism of Innate Immunity at the STAT1 Interface. Cell Reports, Elsevier Inc, 2019, 29 (7), pp.1934-1945.e8. ⟨10.1016/j.celrep.2019.10.020⟩. ⟨pasteur-02868855⟩

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