Phenotypic and Genetic Studies of the Viral Lineage Associated with the Recent Yellow Fever Outbreak in Brazil

Viruses. 2022 Aug 19;14(8):1818. doi: 10.3390/v14081818.

Abstract

Yellow fever virus (YFV) caused an outbreak in the Brazilian Southeast from 2016 to 2019, of the most significant magnitude since the 1900s. 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 2016-2019 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.

Keywords: NS3; NS5; amino acid polymorphisms; southeastern Brazil; virulence; yellow fever virus outbreak.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / genetics
  • Animals
  • Brazil / epidemiology
  • Disease Outbreaks
  • Mice
  • Phenotype
  • Yellow Fever* / epidemiology
  • Yellow fever virus / genetics

Substances

  • Amino Acids

Grants and funding

This work was supported by MCTI/FINEP/FNDCT 01/2016—ZIKA (Grant No. 04.16.0058.00); Preventing and Combating the Zika Virus, MCTIC/FNDCT-CNPq/MEC CAPES/MS-Decit (Grant No. 440865/2016-6). Conselho Nacional de Desenvolvimento Científico e Tecnológico (Grant No. 312446/2018), Preventing and Combating the Zika Virus MCTIC/FNDCT CNPq/MEC-CAPES/MSDecit (Grant No. 88881130684/ 2016-00), INOVA Geração de Conhecimento (Grant No. VPPIS-004-FIO18), Fiocruz, Brazilian National Institute of Science and Technology for Vaccines (INCTV) granted by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)/Fundação de Amparo à Pesquisa do Estado de Minas Gerais (Fapemig)/Coordenação de Aperfeiçoamento de Pessoal: 465293/2014-0; Faperj Programa Cientista do Nosso Estado—2020: CNE2020. MCB was a recipient of the CNPq fellowship for Productivity in Technological Development and Innovative Extension: 308164/2020-2.