BackgroundIn April 2009, a novel swine-derived influenza A virus (H1N1pdm) emerged and rapidly spread around the world, including Japan. It has been suggested that the virus can bind to both 2,3- and 2,6-linked sialic acid receptors in infected mammals, in contrast to contemporary seasonal H1N1 viruses, which have a predilection for 2,6-linked sialic acid.Methods/ResultsTo elucidate the existence and transmissibility of α2,3 sialic acid-specific viruses in H1N1pdm, amino acid substitutions within viral hemagglutinin molecules were investigated, especially D187E, D222G, and Q223R, which are related to a shift from human to avian receptor specificity. Samples from individuals infected during the first and second waves of the outbreak in Japan were examined using a high-throughput sequencing approach. In May 2009, three specimens from mild cases showed D222G and/or Q223R substitutions in a minor subpopulation of viruses infecting these individuals. However, the substitutions almost disappeared in the samples from five mild cases in December 2010. The D187E substitution was not widespread in specimens, even in May 2009.ConclusionsThese results suggest that α2,3 sialic acid-specific viruses, including G222 and R223, existed in humans as a minor population in the early phase of the pandemic, and that D222 and Q223 became more dominant through human-to-human transmission during the first and second waves of the epidemic. These results are consistent with the low substitution rates identified in seasonal H1N1 viruses in 2008.

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Abstrak AbstractBackground: Since a lot of suspected H5N1 cases with severe ARI manifestation were hospitalized and negative for H5N1, it raised a concern to investigate the other etiologies among hospitalized-suspected H5N1 cases. The aim of present study is to investigate the other respiratory pathogens of hospitalized-suspected H5N1 cases in which will provide valuable insight in the etiologies and epidemiology data of ARI.

Tujuan: Mengetahui proporsi kasus SARI yang disebabkan oleh virus infl uenza. Metode yang digunakan untuk mendeteksi keberadaan virus infl uenza adalah metode Reverse Transkriptase-Polymerase Chain Reaction (RT-PCR). Metode: Usap tenggorok yang diambil dari pasien yang memiliki simptom mengarah ke SARI di ekstrak untuk memperoleh RNA, kemudian diamplifi kasi menggunakan 5 pasang primer dan probe (infl uenza A, Infl uenza B, A/H1N1, A/H3N2 dan A/H5N1) dengan metode real-time RT-PCR. Hasil: Dari 549 sampel diketahui bahwa 6% pasien SARI disebabkan oleh virus Infl uenza, dan 4% disebabkan oleh virus Infl uenza A, 2% disebabkan oleh virus Infl uenza B. Virus infl uenza A yang paling banyak menyebabkan SARI adalah virus A/H3N2. Sedangkan 94% dari keseluruhan sampel SARI yang diterima menunjukan hasil negatif terhadap Infl uenza. Kesimpulan: Sebagian besar kasus SARI tidak disebabkan oleh virus infl uenza. Virus infl uenza A yang paling sering menyebabkan SARI adalah A/H3N2. Kondisi bahwa Kasus fl u burung A/H5N1 sudah pernah diidentifi kasi di Indonesia serta penyebaran virus baru infl uenza A/H1N1 pada tahun 2009 meningkatkan kembali pentingnya survelians SARI.

Influenza viruses are a continuous threat to human public health because of their ability to evolve rapidly through genetic drift and reassortment. Three human monoclonal antibodies (HuMAbs) were generated in this study, 1H11, 2H5 and 5G2, and they cross-neutralize a diverse range of group 1 influenza A viruses, including seasonal H1N1, 2009 pandemic H1N1 (H1N1pdm) and avian H5N1 and H9N2. The three HuMAbs were prepared by fusing peripheral blood lymphocytes from an H1N1pdm-infected patient with a newly developed fusion partner cell line, SPYMEG. All the HuMAbs had little hemagglutination inhibition activity but had strong membrane-fusion inhibition activity against influenza viruses. A protease digestion assay showed the HuMAbs targeted commonly a short α-helix region in the stalk of the hemagglutinin. Furthermore, Ile45Phe and Glu47Gly double substitutions in the α-helix region made the HA unrecognizable by the HuMAbs. These two amino acid residues are highly conserved in the HAs of H1N1, H5N1 and H9N2 viruses. The HuMAbs reported here may be potential candidates for the development of therapeutic antibodies against group 1 influenza viruses.