作者: Maki Kiso , Kyoko Shinya , Masayuki Shimojima , Ryo Takano , Kei Takahashi
DOI: 10.1371/JOURNAL.PPAT.1001079
关键词: Virology 、 Microbiology 、 Oseltamivir 、 Zanamivir 、 Pandemic 、 Biology 、 H5N1 genetic structure 、 Viral replication 、 Influenza A virus subtype H5N1 、 Influenza A virus 、 Neuraminidase
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