Phylodynamic pattern and genetic characterization of human influenza A/H3N2 virus in Indonesia from 2008 to 2010

Abstract

Influenza viruses are by nature unstable with high levels of mutations. The sequential accumulation of mutations in the surface glycoproteins allows the virus to evade the neutralizing antibodies. The year-round circulation of H3N2 viruses and the endemicity of H5N1 virus in Indonesia are of serious concern, because the two viruses may reeassort to generate strains with pandemic potential. The consideration of the tropics as the influenza reservoir where viral genetic and antigenic diversity are continually generated and reintroduced into temperate countries makes the study of influenza virus evolution in Indonesia is essential. As only limited data are available, there is an urgent need to monitor the phylodynamic and evolutionary patterns, and the genetic characteristics of the influenza A/H3N2 virus in Indonesia. It is also necessary to evaluate how mutations in hemagglutinin (HA) gene might impact on influenza vaccine efficacy. The present study describes the evolutionary and molecular analyses of HA and neuraminidase (NA) genes and their corresponding encoded proteins of influenza A/H3N2 virus from 2008 to 2010 in Indonesia. It aims to provide insight into the evolutionary pattern and the genetic characteristics of the surface glycoprotein of human influenza A/H3N2 virus in Indonesia, from 2008 to 2010. A total of 100 full-length sequences of HA and NA genes of H3N2 virus were obtained from archived samples of Influenza-Like Illness (ILI) surveillance collected from 2008 to 2010. Phylogenetic and evolutionary analyses showed the dynamics of IndonesianH3N2 virus from 2008 to 2010. Obvious antigenic drift with typical ‘ladder-like’ phylogeny was observed. Multiple lineages were also found in each year, suggesting co-circulation of H3N2 strains at different time periods. The mutations of the Indonesian H3N2 virus were not geographically related. This study confirms that the Indonesian samples had high levels of relative genetic diversity and nucleotide substitution rate. It was also revealed that H3N2 virus had circulated approximately one year before the sampling dates. Major mutations at the antigenic sites A and B of HA protein were identified, while relatively conserved sequences were found at the catalytic sites of NA protein. The mutations at the HA antigenic sites appeared to have influence on the predicted value of vaccine efficacy that emphasizes the need of annual vaccine reformulation based on the circulating viral strain in the corresponding year.