Characterization of oseltamivir-resistant 2009 H1N1 pandemic influenza A viruses.

作者: Maki Kiso , Kyoko Shinya , Masayuki Shimojima , Ryo Takano , Kei Takahashi

DOI: 10.1371/JOURNAL.PPAT.1001079

关键词: VirologyMicrobiologyOseltamivirZanamivirPandemicBiologyH5N1 genetic structureViral replicationInfluenza A virus subtype H5N1Influenza A virusNeuraminidase

摘要: Influenza viruses resistant to antiviral drugs emerge frequently. Not surprisingly, the widespread treatment in many countries of patients infected with 2009 pandemic influenza A (H1N1) neuraminidase (NA) inhibitors oseltamivir and zanamivir has led emergence strains these drugs. Sporadic cases have been associated mutant possessing a histidine-to-tyrosine substitution at position 274 (H274Y) NA, mutation known be responsible for resistance. Here, we characterized vitro vivo properties two pairs oseltaimivir-sensitive -resistant (possessing NA H274Y substitution) H1N1 isolated different parts world. An inhibition assay confirmed that confers resistance viruses. In mouse lungs, found no significant difference replication between oseltamivir-sensitive lungs mice treated or even zanamivir, replicated efficiently. Pathological analysis revealed pathogenicities oseltamivir-resistant were comparable those their counterparts ferrets. Further, transmitted ferrets as efficiently counterparts. Collectively, data indicate pathogenicity transmissibility animal models. Our findings highlight possibility H274Y-possessing could supersede viruses, occurred seasonal

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