Combinatorial mutagenesis of rapidly evolving residues yields super-restrictor antiviral proteins.

Combinatorial mutagenesis of rapidly evolving residues yields super-restrictor antiviral proteins.

Blog Article

Antagonistic interactions drive host-virus evolutionary arms races, which often manifest as recurrent amino acid changes (i.e., positive selection) at their protein-protein interaction interfaces.Here, we investigated whether combinatorial mutagenesis of click here positions under positive selection in a host antiviral protein could enhance its restrictive properties.We tested approximately 700 variants of human MxA, generated by combinatorial mutagenesis, for their ability to restrict Thogotovirus (THOV).

We identified MxA super-restrictors with increased binding to the THOV nucleoprotein (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.Our findings reveal a means to elicit super-restrictor antiviral proteins by leveraging signatures blackmores ache relief focus review of positive selection.Although some MxA super-restrictors of THOV were impaired in their restriction of H5N1 influenza A virus (IAV), other super-restrictor variants increased THOV restriction without impairment of IAV restriction.Thus, broadly acting antiviral proteins such as MxA mitigate breadth-versus-specificity trade-offs that could otherwise constrain their adaptive landscape.