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Poxviruses and paramyxoviruses use a conserved mechanism of STAT1 antagonism to inhibit interferon signaling

DOI: 10.1016/j.chom.2022.01.014 DOI Help

Authors: Callum Talbot-Cooper (University of Cambridge) , Teodors Pantelejevs (University of Cambridge; Latvian Institute of Organic Synthesis) , John P. Shannon (University of Cambridge; NIAD, NIH) , Christian R. Cherry (NIAD, NIH) , Marcus T. Au (University of Cambridge) , Marko Hyvonen (University of Cambridge) , Heather D. Hickman (NIAD, NIH) , Geoffrey L. Smith (University of Cambridge)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Cell Host & Microbe , VOL 296

State: Published (Approved)
Published: February 2022
Diamond Proposal Number(s): 25402

Open Access Open Access

Abstract: The induction of interferon (IFN)-stimulated genes by STATs is a critical host defense mechanism against virus infection. Here, we report that a highly expressed poxvirus protein, 018, inhibits IFN-induced signaling by binding to the SH2 domain of STAT1, thereby preventing the association of STAT1 with an activated IFN receptor. Despite encoding other inhibitors of IFN-induced signaling, a poxvirus mutant lacking 018 was attenuated in mice. The 2.0 Å crystal structure of the 018:STAT1 complex reveals a phosphotyrosine-independent mode of 018 binding to the SH2 domain of STAT1. Moreover, the STAT1-binding motif of 018 shows similarity to the STAT1-binding proteins from Nipah virus, which, similar to 018, block the association of STAT1 with an IFN receptor. Overall, these results uncover a conserved mechanism of STAT1 antagonism that is employed independently by distinct virus families.

Journal Keywords: poxvirus; paramyxovirus; vaccinia virus; Nipah virus; immune evasion; IFN signaling; STAT1; virulence factor; co-structure; convergent evolution

Diamond Keywords: Viruses; Nipah Virus (NiV); Henipaviruses; Vaccinia Virus

Subject Areas: Biology and Bio-materials

Instruments: I04-Macromolecular Crystallography

Added On: 23/02/2022 09:24


Discipline Tags:

Pathogens Infectious Diseases Disease in the Developing World Health & Wellbeing Genetics Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)