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PLoS One ; 6(4): e18956, 2011 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-21572517

RESUMO

BACKGROUND: Pandemic influenza A(H1N1) virus infection quickly circulated worldwide in 2009. In Japan, the first case was reported in May 2009, one month after its outbreak in Mexico. Thereafter, A(H1N1) infection spread widely throughout the country. It is of great importance to profile and understand the situation regarding viral mutations and their circulation in Japan to accumulate a knowledge base and to prepare clinical response platforms before a second pandemic (pdm) wave emerges. METHODOLOGY: A total of 253 swab samples were collected from patients with influenza-like illness in the Osaka, Tokyo, and Chiba areas both in May 2009 and between October 2009 and January 2010. We analyzed partial sequences of the hemagglutinin (HA) and neuraminidase (NA) genes of the 2009 pdm influenza virus in the collected clinical samples. By phylogenetic analysis, we identified major variants of the 2009 pdm influenza virus and critical mutations associated with severe cases, including drug-resistance mutations. RESULTS AND CONCLUSIONS: Our sequence analysis has revealed that both HA-S220T and NA-N248D are major non-synonymous mutations that clearly discriminate the 2009 pdm influenza viruses identified in the very early phase (May 2009) from those found in the peak phase (October 2009 to January 2010) in Japan. By phylogenetic analysis, we found 14 micro-clades within the viruses collected during the peak phase. Among them, 12 were new micro-clades, while two were previously reported. Oseltamivir resistance-related mutations, i.e., NA-H275Y and NA-N295S, were also detected in sporadic cases in Osaka and Tokyo.


Assuntos
Vírus da Influenza A Subtipo H1N1/genética , Influenza Humana/virologia , Mutação , Proteínas Virais/genética , Sequência de Aminoácidos , Substituição de Aminoácidos , Antivirais/farmacologia , Teorema de Bayes , Análise por Conglomerados , Análise Mutacional de DNA , Farmacorresistência Viral/genética , Hemaglutininas Virais/química , Hemaglutininas Virais/classificação , Hemaglutininas Virais/genética , Humanos , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Influenza Humana/epidemiologia , Japão/epidemiologia , Modelos Moleculares , Dados de Sequência Molecular , Neuraminidase/química , Neuraminidase/classificação , Neuraminidase/genética , Oseltamivir/farmacologia , Pandemias , Filogenia , Conformação Proteica , Multimerização Proteica , Estações do Ano , Proteínas Virais/química , Proteínas Virais/classificação
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