Poxviruses and paramyxoviruses use a conserved mechanism of STAT1 antagonism to inhibit interferon signaling.
Shannon, John P
Cherry, Christian R
Au, Marcus T
Hickman, Heather D
Cell Host Microbe
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Talbot-Cooper, C., Pantelejevs, T., Shannon, J. P., Cherry, C. R., Au, M. T., Hyvönen, M., Hickman, H. D., & et al. (2022). Poxviruses and paramyxoviruses use a conserved mechanism of STAT1 antagonism to inhibit interferon signaling.. Cell Host Microbe https://doi.org/10.1016/j.chom.2022.01.014
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.
Wellcome Trust (090315/B/09/A)
Biotechnology and Biological Sciences Research Council (1804930)
Wellcome Trust (090315/Z/09/Z)
External DOI: https://doi.org/10.1016/j.chom.2022.01.014
This record's URL: https://www.repository.cam.ac.uk/handle/1810/333482
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/