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Amino Acid Polymorphisms on the Brazilian Strain of Yellow Fever Virus Methyltransferase Are Related to the Host's Immune Evasion Mediated by Type I Interferon.
Furtado, Nathália Dias; de Mello, Iasmim Silva; de Godoy, Andre Schutzer; Noske, Gabriela Dias; Oliva, Glaucius; Canard, Bruno; Decroly, Etienne; Bonaldo, Myrna C.
Afiliación
  • Furtado ND; Laboratório de Biologia Molecular de Flavivírus, Instituto Oswaldo Cruz-Fiocruz, Rio de Janeiro 21040-900, Brazil.
  • de Mello IS; Laboratório de Biologia Molecular de Flavivírus, Instituto Oswaldo Cruz-Fiocruz, Rio de Janeiro 21040-900, Brazil.
  • de Godoy AS; Centro de Pesquisa e Inovação em Biodiversidade e Fármacos, Instituto de Física de São Carlos-USP, São Paulo 13563-120, Brazil.
  • Noske GD; Centro de Pesquisa e Inovação em Biodiversidade e Fármacos, Instituto de Física de São Carlos-USP, São Paulo 13563-120, Brazil.
  • Oliva G; Centro de Pesquisa e Inovação em Biodiversidade e Fármacos, Instituto de Física de São Carlos-USP, São Paulo 13563-120, Brazil.
  • Canard B; Architecture et Fonction des Macromolécules Biologiques, Aix-Marseille Université, CNRS, UMR7257, 13009 Marseille, France.
  • Decroly E; Architecture et Fonction des Macromolécules Biologiques, Aix-Marseille Université, CNRS, UMR7257, 13009 Marseille, France.
  • Bonaldo MC; Laboratório de Biologia Molecular de Flavivírus, Instituto Oswaldo Cruz-Fiocruz, Rio de Janeiro 21040-900, Brazil.
Viruses ; 15(1)2023 01 10.
Article en En | MEDLINE | ID: mdl-36680231
Since late 2016, a yellow fever virus (YFV) variant carrying a set of nine amino acid variations has circulated in South America. Three of them were mapped on the methyltransferase (MTase) domain of viral NS5 protein. To assess whether these changes affected viral infectivity, we synthesized YFV carrying the MTase of circulating lineage as well as its isoform with the residues of the previous strains (NS5 K101R, NS5 V138I, and NS5 G173S). We observed a slight difference in viral growth properties and plaque phenotype between the two synthetic YFVs. However, the MTase polymorphisms associated with the Brazilian strain of YFV (2016-2019) confer more susceptibility to the IFN-I. In addition, in vitro MTase assay revealed that the interaction between the YFV MTase and the methyl donor molecule (SAM) is altered in the Brazilian MTase variant. Altogether, the results reported here describe that the MTase carrying the molecular signature of the Brazilian YFV circulating since 2016 might display a slight decrease in its catalytic activity but virtually no effect on viral fitness in the parameters comprised in this study. The most marked influence of these residues stands in the immune escape against the antiviral response mediated by IFN-I.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Virus de la Fiebre Amarilla / Interferón Tipo I País/Región como asunto: America do sul / Brasil Idioma: En Revista: Viruses Año: 2023 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Virus de la Fiebre Amarilla / Interferón Tipo I País/Región como asunto: America do sul / Brasil Idioma: En Revista: Viruses Año: 2023 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Suiza