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An investigation of the circulating virus revealed that most of the genomes detected in this period carried nine unique amino acid polymorphisms, with eight located in the non-structural proteins NS3 and NS5, which are pivotal for viral replication. To elucidate the effect of these amino acid changes on viral infection, we constructed viruses carrying amino acid alterations in NS3 and NS5, performed infection in different cells, and assessed their neurovirulence in BALB\/c mice and infected AG129 mice. We observed that the residues that compose the YFV 2016\u20132019 molecular signature in the NS5 protein might have been related to an attenuated phenotype, and that the alterations in the NS3 protein only slightly affected viral infection in AG129 mice, increasing to a low extent the mortality rate of these animals. These results contributed to unveiling the role of specific naturally occurring amino acid changes in the circulating strain of YFV in Brazil.<\/jats:p>","DOI":"10.3390\/v14081818","type":"journal-article","created":{"date-parts":[[2022,8,22]],"date-time":"2022-08-22T01:56:40Z","timestamp":1661133400000},"page":"1818","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Phenotypic and Genetic Studies of the Viral Lineage Associated with the Recent Yellow Fever Outbreak in Brazil"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6657-1397","authenticated-orcid":false,"given":"Nath\u00e1lia Dias","family":"Furtado","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Biology of Flaviviruses, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 21040-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5740-9005","authenticated-orcid":false,"given":"Mariela Mart\u00ednez","family":"G\u00f3mez","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology of Flaviviruses, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 21040-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iasmim Silva","family":"de Mello","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology of Flaviviruses, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 21040-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D\u00e9berli Ruiz","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology of Flaviviruses, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 21040-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9899-3386","authenticated-orcid":false,"given":"Myrna Cristina","family":"Bonaldo","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology of Flaviviruses, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 21040-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1016\/j.tim.2018.05.012","article-title":"Yellow Fever Virus: Knowledge Gaps Impeding the Fight Against an Old Foe","volume":"26","author":"Douam","year":"2018","journal-title":"Trends Microbiol."},{"key":"ref_2","unstructured":"Franco, O. 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