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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\u20132019) 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.<\/jats:p>","DOI":"10.3390\/v15010191","type":"journal-article","created":{"date-parts":[[2023,1,10]],"date-time":"2023-01-10T01:30:47Z","timestamp":1673314247000},"page":"191","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Amino Acid Polymorphisms on the Brazilian Strain of Yellow Fever Virus Methyltransferase Are Related to the Host\u2019s Immune Evasion Mediated by Type I Interferon"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6657-1397","authenticated-orcid":false,"given":"Nath\u00e1lia Dias","family":"Furtado","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Biologia Molecular de Flaviv\u00edrus, Instituto Oswaldo Cruz-Fiocruz, Rio de Janeiro 21040-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iasmim Silva","family":"de Mello","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Molecular de Flaviv\u00edrus, Instituto Oswaldo Cruz-Fiocruz, Rio de Janeiro 21040-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0613-9164","authenticated-orcid":false,"given":"Andre Schutzer","family":"de Godoy","sequence":"additional","affiliation":[{"name":"Centro de Pesquisa e Inova\u00e7\u00e3o em Biodiversidade e F\u00e1rmacos, Instituto de F\u00edsica de S\u00e3o Carlos-USP, S\u00e3o Paulo 13563-120, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela Dias","family":"Noske","sequence":"additional","affiliation":[{"name":"Centro de Pesquisa e Inova\u00e7\u00e3o em Biodiversidade e F\u00e1rmacos, Instituto de F\u00edsica de S\u00e3o Carlos-USP, S\u00e3o Paulo 13563-120, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2719-0302","authenticated-orcid":false,"given":"Glaucius","family":"Oliva","sequence":"additional","affiliation":[{"name":"Centro de Pesquisa e Inova\u00e7\u00e3o em Biodiversidade e F\u00e1rmacos, Instituto de F\u00edsica de S\u00e3o Carlos-USP, S\u00e3o Paulo 13563-120, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno","family":"Canard","sequence":"additional","affiliation":[{"name":"Architecture et Fonction des Macromol\u00e9cules Biologiques, Aix-Marseille Universit\u00e9, CNRS, UMR7257, 13009 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6046-024X","authenticated-orcid":false,"given":"Etienne","family":"Decroly","sequence":"additional","affiliation":[{"name":"Architecture et Fonction des Macromol\u00e9cules Biologiques, Aix-Marseille Universit\u00e9, CNRS, UMR7257, 13009 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9899-3386","authenticated-orcid":false,"given":"Myrna C.","family":"Bonaldo","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Molecular de Flaviv\u00edrus, Instituto Oswaldo Cruz-Fiocruz, Rio de Janeiro 21040-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.3201\/eid1009.040197","article-title":"Genetic divergence and dispersal of yellow fever virus, Brazil","volume":"10","author":"Vasconcelos","year":"2004","journal-title":"Emerg. 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