Heterozygous and generalist MxA super-restrictors overcome breadth-specificity tradeoffs in antiviral restriction.

ABSTRACT: Antiviral restriction factors such as MxA (myxovirus resistance protein A) inhibit a broad range of viruses. However, they face the challenge of maintaining this breadth as viruses evolve to escape their defense. Viral escape drives restriction factors to evolve rapidly, selecting for amino acid changes at their virus-binding interfaces to regain defense. How do restriction factors balance the breadth of antiviral functions against the need to evolve specificity against individual escaping viruses? We explored this question in human MxA, which uses its rapidly evolving loop L4 as the specificity determinant for orthomyxoviruses such as THOV and IAV. Previous combinatorial mutagenesis of rapidly evolving residues in human MxA loop L4 revealed variants with a ten-fold increase in pote

SUBMITTER: Geiger RA 

PROVIDER: S-EPMC11482965 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature