Convergent evolution of escape from hepaciviral antagonism in primates.

摘要: The ability to mount an interferon response on sensing viral infection is a critical component of mammalian innate immunity. Several viruses directly antagonize pathways block activation the host immune response. Here, we show that recurrent antagonism has shaped evolution protein MAVS--a crucial viral-sensing pathway in primates. From sequencing and phylogenetic analyses MAVS from 21 simian primates, found evolved under strong positive selection. We focused how this selection MAVS' susceptibility Hepatitis C virus (HCV). functionally tested proteins diverse primate species for their resist by HCV, which uses its protease NS3/4A cleave human MAVS. multiple primates are resistant inhibition HCV protease. This resistance maps single changes within cleavage site MAVS, protect getting cleaved Remarkably, most these have been independently acquired at residue 506 "escape" mutations lower affinity NS3 allow it better restrict replication. further proteases all other hepaciviruses, including highly divergent GBV-A GBV-C viruses, similar HCV. conclude convergent resulted escape hepaciviruses. Our study provides model whereby insights into ancient history infections can be gained using extant genes. also provide means might clear hepaciviruses like