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

Cell Host Microbe. 2022 Feb 16:S1931-3128(22)00050-6. doi: 10.1016/j.chom.2022.01.014. Online ahead of print.ABSTRACTThe 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.PMID:35182467 | DOI:10.1016/j.chom.2022.01.014

Source: Cell Host and Microbe - February 19, 2022 Category: Microbiology Authors: Callum Talbot-Cooper Teodors Pantelejevs John P Shannon Christian R Cherry Marcus T Au Marko Hyv önen Heather D Hickman Geoffrey L Smith Source Type: research