College of Global Change and Earth System Science, Beijing Normal University, Beijing, China.
Department of Developmental Cell Biology, China Medical University, Shenyang, China.
J Med Virol. 2022 Sep;94(9):4406-4416. doi: 10.1002/jmv.27870. Epub 2022 Jun 1.
H1N1 influenza has brought serious threats to people's health and a high socioeconomic burden to society. Oseltamivir, a kind of neuraminidase (NA) inhibitor, is the second-generation specific drug that is broadly used currently. However, H1N1 influenza viruses have exhibited oseltamivir resistance in the past decades, which might be a hidden danger. To understand the frequency and distribution laws of oseltamivir-resistant viruses, we conducted a thorough and deep analysis of the available NA protein sequences of H1N1 influenza viruses worldwide from 1918 to 2020. The differences and similarities before and after 2009 were also considered since the dominant viruses changed in this period. Results showed that 3.76% of H1N1 viruses harbored oseltamivir resistance currently. Among various significative mutations, H274Y had the highest frequency of 3.30%, while the frequencies of the other mutations were far below this whether before or after 2009. The oseltamivir resistance was mainly found in three hosts, humans, swine, and avian. Different mutation sites could exhibit different distributions in each host. Our results showed that the resistance level reached a peak during the 2007-2008 influenza season and then quickly decreased in 2009. The resistance also displayed a global distribution. The densely populated countries usually had a high resistance level. However, frequent significative mutations were also found in some small countries. Our findings indicated the necessity of monitoring oseltamivir resistance around the world. The study could provide a unique perspective toward the cognition of viruses and facilitate the future study of both pandemic and drug development.
H1N1 流感对人们的健康构成了严重威胁,并给社会带来了巨大的经济负担。奥司他韦(Oseltamivir)是一种神经氨酸酶(NA)抑制剂,是目前广泛使用的第二代特异性药物。然而,H1N1 流感病毒在过去几十年中已经表现出对奥司他韦的耐药性,这可能是一个隐患。为了了解奥司他韦耐药病毒的频率和分布规律,我们对 1918 年至 2020 年全球范围内的 H1N1 流感病毒的可用 NA 蛋白序列进行了深入和全面的分析。由于在此期间主要病毒发生了变化,我们还考虑了 2009 年前后的差异和相似之处。结果表明,目前有 3.76%的 H1N1 病毒携带奥司他韦耐药性。在各种有意义的突变中,H274Y 的频率最高,为 3.30%,而无论是在 2009 年之前还是之后,其他突变的频率都远低于此。奥司他韦耐药性主要在三种宿主中发现,包括人类、猪和禽类。不同的突变位点在每个宿主中可能表现出不同的分布。我们的结果表明,耐药水平在 2007-2008 流感季节达到峰值,然后在 2009 年迅速下降。耐药性也呈现出全球性分布。人口密集的国家通常耐药水平较高。然而,在一些小国家也发现了频繁的有意义突变。我们的研究结果表明,有必要在全球范围内监测奥司他韦耐药性。该研究可以为了解病毒提供独特的视角,并有助于未来对大流行和药物开发的研究。