GEPHE SUMMARY Print
Entry Status
Published
GepheID
GP00001455
Main curator
Prigent
PHENOTYPIC CHANGE
Trait Category
Trait State in Taxon A
Common woolly monkey and others
Trait State in Taxon B
Dusky titi monkey
Ancestral State
Taxon A
Taxonomic Status
Taxon A
Common Name
brown woolly monkey
Synonyms
Lagothrix lagotricha lagotricha; Simia lagotricha; brown woolly monkey; Humboldt's woolly monkey; common woolly monkey; Lagothrix lagotricha (Humboldt, 1812); Lagothrix lagothricha
Rank
species
Lineage
Show more ... mi; Sarcopterygii; Dipnotetrapodomorpha; Tetrapoda; Amniota; Mammalia; Theria; Eutheria; Boreoeutheria; Euarchontoglires; Primates; Haplorrhini; Simiiformes; Platyrrhini; Atelidae; Atelinae; Lagothrix
NCBI Taxonomy ID
is Taxon A an Infraspecies?
No
Taxon B
Common Name
red-bellied titi
Synonyms
Callicebus moloch; red-bellied titi; Dusky titi; Callicebus moloch Hoffmannsegg, 1807
Rank
species
Lineage
Show more ... erygii; Dipnotetrapodomorpha; Tetrapoda; Amniota; Mammalia; Theria; Eutheria; Boreoeutheria; Euarchontoglires; Primates; Haplorrhini; Simiiformes; Platyrrhini; Pitheciidae; Callicebinae; Plecturocebus
NCBI Taxonomy ID
is Taxon B an Infraspecies?
No
GENOTYPIC CHANGE
Generic Gene Name
MAVS
Synonyms
IPS1; VISA; IPS-1; CARDIF; KIAA1271
Sequence Similarities
-
GO - Biological Process
GO:0045087 : innate immune response ... show more
UniProtKB
Homo sapiens
GenebankID or UniProtKB
Presumptive Null
No
Molecular Type
Aberration Type
SNP
SNP Coding Change
Nonsynonymous
Molecular Details of the Mutation
Val506Ala resistant to cleavage
Experimental Evidence
Taxon A Taxon B Position
Codon - - -
Amino-acid - - -
Authors
Patel MR; Loo YM; Horner SM; Gale M; Malik HS
Abstract
The ability to mount an interferon response on sensing viral infection is a critical component of mammalian innate immunity. Several viruses directly antagonize viral sensing pathways to block activation of the host immune response. Here, we show that recurrent viral antagonism has shaped the evolution of the host protein MAVS--a crucial component of the viral-sensing pathway in primates. From sequencing and phylogenetic analyses of MAVS from 21 simian primates, we found that MAVS has evolved under strong positive selection. We focused on how this positive selection has shaped MAVS' susceptibility to Hepatitis C virus (HCV). We functionally tested MAVS proteins from diverse primate species for their ability to resist antagonism by HCV, which uses its protease NS3/4A to cleave human MAVS. We found that MAVS from multiple primates are resistant to inhibition by the HCV protease. This resistance maps to single changes within the protease cleavage site in MAVS, which protect MAVS from getting cleaved by the HCV protease. Remarkably, most of these changes have been independently acquired at a single residue 506 that evolved under positive selection. We show that "escape" mutations lower affinity of the NS3 protease for MAVS and allow it to better restrict HCV replication. We further show that NS3 proteases from all other primate hepaciviruses, including the highly divergent GBV-A and GBV-C viruses, are functionally similar to HCV. We conclude that convergent evolution at residue 506 in multiple primates has resulted in escape from antagonism by hepaciviruses. Our study provides a model whereby insights into the ancient history of viral infections in primates can be gained using extant host and virus genes. Our analyses also provide a means by which primates might clear infections by extant hepaciviruses like HCV.
Additional References
RELATED GEPHE
Related Genes
No matches found.
Related Haplotypes
1
EXTERNAL LINKS
COMMENTS
mutation confers resistance to NS3/4A viral protease as observed in biochemical test
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