Abstract

Noroviruses (NoVs) are the major cause of acute gastroenteritis outbreaks, and, despite a wide genetic diversity, genotype II.4 is the most prevalent strain worldwide. Mutations and homologous recombination have been proposed as mechanisms driving the epochal evolution of the GII.4, with the emergence of new variants in 1–3-year intervals causing global epidemics. There are no data reporting the dynamics of GII.4 variants along a specific period in Brazil. Therefore, to improve the understanding of the comportment of these variants in the country, the aim of this study was to evaluate the circulation of NoV GII.4 variants during a 9-year period in 3 out of 5 Brazilian regions. A total of 147 samples were sequenced, and a phylogenetic analysis of subdomain P2 demonstrated the circulation of six GII.4 variants, Asia_2003, Hunter_2004, Den Haag_2006b, Yerseke_2006a, New Orleans_2009, and Sydney_2012, during this period. The most prevalent variant was Den Haag_2006b, circulating in different Brazilian regions from 2006 to 2011. A Bayesian coalescent analysis was used to calculate the mean evolutionary rate of subdomain P2 as 7.3×10−3 (5.85×10−3–8.82×10−3) subst./site/year. These analyses also demonstrated that clade Den Haag_2006b experienced a rapid expansion in 2005 and another in 2008 after a period of decay. The evaluation of the temporal dynamics of NoV GII.4 in Brazil revealed a similar pattern, with few exceptions, to the worldwide observation. These data highlight the importance of surveillance for monitoring the emergence of new strains of NoV GII.4 and its impact on cases of acute gastroenteritis.

Highlights

  • Noroviruses (NoVs) are considered to be the major causative agent of acute gastroenteritis (AGE) outbreaks worldwide [1]

  • Variants Circulating in Brazil An Maximum Likelihood (ML) phylogenetic analysis of the subdomain P2 of gene encoding VP1 from 147 NoV GII.4

  • NoV GII.4 is the most prevalent genotype of NoV is associated with worldwide acute gastroenteritis outbreaks [10,11,14,42,55]

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Summary

Introduction

Noroviruses (NoVs) are considered to be the major causative agent of acute gastroenteritis (AGE) outbreaks worldwide [1]. The genome is organized into three open reading frames (ORF), with ORF1 encoding six non-structural proteins, including the RNA-dependent RNA-polymerase, ORF2 encoding the structural protein VP1 that composes the viral capsid, and ORF3 encoding the structural protein VP2 [3]. The protruding P2 domain, located at the most exposed surface of the viral capsid, is the major responsible for the antigenicity of the virus and determines interaction with host cell attachment factors (histo-blood group antigen, HBGA) [4,5]. NoV has been classified into five genogroups on the basis of the VP1 sequence (GI to GV) that can be further subdivided into more than 36 genotypes [6]. A standardization of NoV nomenclature was proposed based on the classification of the VP1 and ORF1 sequences due to the common event of recombination in the hotspot ORF1/ORF2 [7]

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