2016-2019 年中国大陆人感染高致病性禽流感 H7N9 病毒中神经氨酸酶抑制剂耐药性降低的特征和产生。

Profile and generation of reduced neuraminidase inhibitor susceptibility in highly pathogenic avian influenza H7N9 virus from human cases in Mainland of China, 2016-2019.

机构信息

National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, WHO Collaborating Center for Reference and Research on Influenza, Beijing, China.

出版信息

Virology. 2020 Oct;549:77-84. doi: 10.1016/j.virol.2020.07.018. Epub 2020 Aug 8.

DOI:10.1016/j.virol.2020.07.018

PMID:32853849

Abstract

Human infections with highly pathogenic avian influenza (HPAI) H7N9 virus were detected in late 2016. We examined the drug resistance profile of 30 HPAI H7N9 isolates from Mainland of China (2016-2019). Altogether, 23% (7/30) carried neuraminidase inhibitors (NAIs) - resistance mutations, and 13% (4/30) displayed reduced susceptibility to NAIs in neuraminidase (NA) inhibition test. An HPAI H7N9 reassortment virus we prepared was passaged with NAIs for 10 passages. Passage with zanamivir induced an E119G substitution in NA, whereas passage with oseltamivir induced R292K and E119V substitutions that simulated that seen in oseltamivir -treated HPAI H7N9 cases, indicating that the high frequency of resistant strains in the HPAI H7N9 isolates is related to NAIs use. In presence of NAIs, R238I, A146E, G151E and G234T substitutions were found in HA1 region of HA. No amino acid mutations were found in the internal genes of the recombinant virus.

摘要

人感染高致病性禽流感（HPAI）H7N9 病毒于 2016 年末被发现。我们检测了来自中国大陆的 30 株 HPAI H7N9 分离株的耐药性特征（2016-2019）。共有 23%（7/30）的分离株携带神经氨酸酶抑制剂（NAI）耐药突变，13%（4/30）的分离株在神经氨酸酶（NA）抑制试验中对 NAI 的敏感性降低。我们制备的一株 HPAI H7N9 重配病毒经过 10 代 NAI 传代。扎那米韦传代诱导 NA 中的 E119G 取代，而奥司他韦传代诱导 R292K 和 E119V 取代，模拟了奥司他韦治疗的 HPAI H7N9 病例中的情况，表明 HPAI H7N9 分离株中高频率的耐药株与 NAI 的使用有关。在 NAI 存在的情况下，在 HA1 区域的 HA 中发现了 R238I、A146E、G151E 和 G234T 取代。重组病毒的内部基因未发现氨基酸突变。