Abstract

Since the beginning of the XXI Century, the yellow fever virus (YFV) has been cyclically spreading from the Amazon basin to Brazil’s South and Southeast regions, culminating in an unprecedented outbreak that started in 2016. In this work, we studied four YFV isolated from non-human primates obtained during outbreaks in the states of Rio Grande do Sul in 2008 (PR4408), Goiás (GO05), and Espírito Santo (ES-504) in 2017, and Rio de Janeiro (RJ 155) in 2019. These isolates have genomic differences mainly distributed in non-structural proteins. We compared the isolates’ rates of infection in mammal and mosquito cells and neurovirulence in adult mice. RJ 155 and PR4408 YFV isolates exhibited higher infectivity in mammalian cells and neurovirulence in mice. In mosquito Aag2 cells, GO05 and PR4408 displayed the lowest proliferation rates. These results suggest that RJ 155 and PR4408 YFV isolates carry some genomic markers that increase infectivity in mammal hosts. From this characterization, it is possible to contribute to discovering new molecular markers for the virulence of YFV.

Highlights

  • Yellow fever virus (YFV) is the prototype member of the genus Flavivirus, which comprises other arthropod-borne viruses of clinical relevance

  • yellow fever virus (YFV) Espírito Santo (ES)-504 was isolated from an NHP found dead in ES in February 2017 (Bonaldo et al, 2017), and Rio de Janeiro (RJ) 155 was collected in January 2019 in RJ (Abreu et al, 2019), both located in southeastern Brazil

  • ES-504, PR4408, and GO05 isolates were isolated in C6/36 cells, and RJ 155 was isolated in Vero cells

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Summary

INTRODUCTION

Yellow fever virus (YFV) is the prototype member of the genus Flavivirus (family Flaviviridae), which comprises other arthropod-borne viruses of clinical relevance. There were 2,523 epizootics, and 2,155 confirmed human cases (case fatality rate of 34.4%) from July 2016 to October 2018 in the states of Minas Gerais, São Paulo, Espírito Santo (ES), and Rio de Janeiro (RJ), all four states located in the southeastern region (Brasil, 2017, 2018). In this occasion, the Brazilian Health Ministry recommended the vaccination of the population in states without vaccine coverage in the Southeast, in the South and some localities in the Northeast until 2019 (Mendes, 2018). We evaluated and compared the infectivity dynamics of these four YFV strains in cell culture and the neurovirulence in BALB/c mice in order to establish if there were any differences in viral replicative fitness between the YFV 2000–2010 and YFV 2016– 2019 groups

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