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PHYLOGENETIC ANALYSES OF INFLUENZA A (H1N1)PDM09 HEMAGGLUTININ GENE DURING AND AFTER THE PANDEMIC EVENT IN BRAZIL
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Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratório e do Sarampo. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratório e do Sarampo. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratório e do Sarampo. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratório e do Sarampo. Rio de Janeiro, RJ, Brasil / Centre International de Recherche en Infectologie (CIRI). Fondation Mérieux. Emerging Pathogens Laboratory. Lyon, France.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratório e do Sarampo. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratório e do Sarampo. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratório e do Sarampo. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratório e do Sarampo. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratório e do Sarampo. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratório e do Sarampo. Rio de Janeiro, RJ, Brasil / Centre International de Recherche en Infectologie (CIRI). Fondation Mérieux. Emerging Pathogens Laboratory. Lyon, France.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratório e do Sarampo. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratório e do Sarampo. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratório e do Sarampo. Rio de Janeiro, RJ, Brasil.
Abstract
Pandemic influenza A H1N1 [A(H1N1)pdm09] was first detected in Brazil in May 2009, and spread extensively
throughout the country causing a peak of infection during June to August 2009. Since then, it has continued to
circulate with a seasonal pattern, causing high rates of morbidity and mortality. Over this period, the virus has
continually evolved with the accumulation of new mutations. In this study we analyze the phylogenetic relationship
in a collection of 220 A(H1N1)pdm09 hemagglutinin (HA) gene sequences collected during and after the
pandemic period (2009 to 2014) in Brazil. In addition, we have looked for evidence of viral polymorphisms associated
with severe disease and compared the range of viral variants with the vaccine strain (A/California/7/2009)
used throughout this period.
The phylogenetic analyses in this study revealed the circulation of at least eight genetic groups in Brazil. Two (G6-
pdm and G7-pdm) co-circulated during the pandemic period, showing an early pattern of viral diversification
with a low genetic distance from vaccine strain. Other phylogenetic groups, G5, G6 (including 6B, 6C and 6D subgroups),
and G7 were found in the subsequent epidemic seasons from 2011 to 2014. These viruses exhibited
more amino acid differences from the vaccine strain with several substitutions at the antigenic sites. This is
associated with a theoretical decrease in the vaccine efficacy. Furthermore, we observed that the presence of
any polymorphism at residue 222 of the HA gene was significantly associated with severe/fatal cases, reinforcing
previous reports that described this residue as a potential virulence marker.
This study provides new information about the circulation of some viral variants in Brazil, follows up potential
genetic markers associated with virulence and allows infer if the efficacy of the current vaccine against more
recent A(H1N1)pdm09 strains may be reduced.
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