Institute of Pathogenic Microbiology, NHC Key Laboratories of Enteric Pathogenic Microbiology, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, 210009, China.
Institute of Pathogenic Microbiology, NHC Key Laboratories of Enteric Pathogenic Microbiology, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, 210009, China.
Virology. 2019 Oct;536:58-67. doi: 10.1016/j.virol.2019.08.004. Epub 2019 Aug 6.
Human infection with H7N9 virus has provoked global public health concern due to the substantial morbidity and mortality. Neuraminidase inhibitors (NAIs) are used as first-line drugs to treat the infection. However, virus quasispecies can evolve rapidly under drug pressure, which may alter various biological characteristics of virus. Using an in vitro evolution platform and next-generation sequencing, we found the presence of peramivir led to changes to the dominant populations of the virus. Two important amino acid substitutions were identified in NA, I222T and H274Y, which caused reduced susceptibilities to oseltamivir or both oseltamivir and peramivir as confirmed by enzyme- and cell-based assays. The NA-H274Y variant showed decreased replicative fitness at the early stage of infection accompanied with impaired NA function. The quasispecies evolution of H7N9 virus and the potential emergence of these two variants should be closely monitored, which may guide the adjustment of antiviral strategies.
人感染 H7N9 病毒引起了全球公共卫生关注，因为它发病率和死亡率都很高。神经氨酸酶抑制剂（NAIs）被用作治疗感染的一线药物。然而，病毒准种在药物压力下可以迅速进化，这可能改变病毒的各种生物学特性。我们使用体外进化平台和下一代测序发现，金刚烷胺的存在导致病毒的主要种群发生变化。在 NA 中发现了两个重要的氨基酸取代，I222T 和 H274Y，这导致对奥司他韦或奥司他韦和帕拉米韦的敏感性降低，这通过酶和细胞测定得到证实。NA-H274Y 变体在感染的早期阶段显示出复制适应性降低，同时伴随 NA 功能受损。H7N9 病毒的准种进化和这两种变体的出现应该密切监测，这可能指导抗病毒策略的调整。
