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• W3101545900 abstract "Host-virus evolutionary arms-races are driven by antagonistic interactions and often manifest as recurrent amino acid changes (i.e., positive selection) at their protein-protein interaction interfaces. Here, we investigated whether combinatorial mutagenesis of positions under positive selection in a host antiviral protein could enhance its restrictive properties. We tested ∼ 800 variants of the human MxA protein, generated by combinatorial mutagenesis, for their ability to restrict Thogoto orthomyxovirus (THOV). We identified MxA ‘super-restrictors’ with increased binding to THOV NP target protein and 10-fold higher anti-THOV restriction relative to wild-type human MxA, the most potent naturally-occurring anti-THOV restrictor identified. However, MxA super-restrictors of THOV were impaired in their restriction of influenza A virus. Our findings thus reveal a breadth-versus-specificity tradeoff that constrains the adaptive landscape of antiviral proteins." @default.
• W3101545900 created "2020-11-23" @default.
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• W3101545900 date "2019-02-22" @default.
• W3101545900 modified "2023-09-23" @default.
• W3101545900 title "Evolution-guided design of super-restrictor antiviral proteins reveals a breadth-versus-specificity tradeoff" @default.
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