1] Department of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, Box 1124, New York, New York 10029, USA [2].
Nat Commun. 2013;4:2854. doi: 10.1038/ncomms3854.
Without baseline human immunity to the emergent avian influenza A(H7N9) virus, neuraminidase inhibitors are vital for controlling viral replication in severe infections. An amino acid change in the viral neuraminidase associated with drug resistance, NA-R292K (N2 numbering), has been found in some H7N9 clinical isolates. Here we assess the impact of the NA-R292K substitution on antiviral sensitivity and viral replication, pathogenicity and transmissibility of H7N9 viruses. Our data indicate that an H7N9 isolate encoding the NA-R292K substitution is highly resistant to oseltamivir and peramivir and partially resistant to zanamivir. Furthermore, H7N9 reassortants with and without the resistance mutation demonstrate comparable viral replication in primary human respiratory cells, virulence in mice and transmissibility in guinea pigs. Thus, in stark contrast to oseltamivir-resistant seasonal influenza A(H3N2) viruses, H7N9 virus replication and pathogenicity in these models are not substantially altered by the acquisition of high-level oseltamivir resistance due to the NA-R292K mutation.
由于人类对新出现的禽流感 A(H7N9)病毒没有基线免疫力，神经氨酸酶抑制剂对于控制严重感染中的病毒复制至关重要。在一些 H7N9 临床分离株中发现了与耐药性相关的病毒神经氨酸酶中的一个氨基酸变化，即 NA-R292K（N2 编号）。在这里，我们评估了 NA-R292K 取代对 H7N9 病毒的抗病毒敏感性、病毒复制、致病性和传染性的影响。我们的数据表明，编码 NA-R292K 取代的 H7N9 分离株对奥司他韦和帕拉米韦高度耐药，对扎那米韦部分耐药。此外，具有和不具有耐药突变的 H7N9 重配体在原代人呼吸道细胞中显示出相当的病毒复制、在小鼠中的毒力和在豚鼠中的传染性。因此，与奥司他韦耐药的季节性流感 A(H3N2)病毒形成鲜明对比的是，由于 NA-R292K 突变导致高水平奥司他韦耐药，这些模型中 H7N9 病毒的复制和致病性并没有发生实质性改变。
