title: Arbovirus high fidelity variant loses fitness in mosquitoes and mice.
abstract: The error rate of RNA-dependent RNA polymerases (RdRp) affects the mutation frequency in a population of viral RNAs. Using chikungunya virus (CHIKV), we describe a unique arbovirus fidelity variant with a single C483Y amino acid change in the nsP4 RdRp that increases replication fidelity and generates populations with reduced genetic diversity. In mosquitoes, high fidelity CHIKV presents lower infection and dissemination titers than wild type. In newborn mice, high fidelity CHIKV produces truncated viremias and lower organ titers. These results indicate that increased replication fidelity and reduced genetic diversity negatively impact arbovirus fitness in invertebrate and vertebrate hosts.
authors: Institut Pasteur, Viral Populations and Pathogenesis, Centre National de la Recherche Scientifique, Unité de Recherche Associée 3015, 75724 Paris Cedex 15, France.
authors: Lark L
authors: LL
authors: Coffey
authors: Yasnee
authors: Y
authors: Beeharry
authors: Antonio V
authors: AV
authors: Bordería
authors: Hervé
authors: H
authors: Blanc
authors: Marco
authors: M
authors: Vignuzzi
mesh_terms: D018354:Alphavirus Infections / Q000097:blood / Q000821:virology*; D019943:Amino Acid Substitution; D000818:Animals; D000831:Animals, Newborn; D001103:Arboviruses / Q000235:genetics / Q000472:pathogenicity; D002460:Cell Line; D002646:Chikungunya virus / Q000235:genetics* / Q000472:pathogenicity; D009033:Culicidae / Q000821:virology*; D014644:Genetic Variation; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D059645:Mutation Rate; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics; D013045:Species Specificity; D014766:Viremia / Q000235:genetics; D014774:Virulence / Q000235:genetics; D014779:Virus Replication / Q000235:genetics
chemical_list: D012324:RNA-Dependent RNA Polymerase