tetano
Editor, Senior Moderator
Virology. 2019 Aug 6;536:58-67. doi: 10.1016/j.virol.2019.08.004. [Epub ahead of print]
[h=1]The evolution and characterization of influenza A(H7N9) virus under the selective pressure of peramivir.[/h] Ge Y[SUP]1[/SUP], Chi Y[SUP]2[/SUP], Min X[SUP]3[/SUP], Zhao K[SUP]2[/SUP], Wu B[SUP]2[/SUP], Wu T[SUP]2[/SUP], Zhu X[SUP]2[/SUP], Shi Z[SUP]2[/SUP], Zhu F[SUP]2[/SUP], Cui L[SUP]4[/SUP].
[h=3]Author information[/h] 1 Institute of Pathogenic Microbiology, NHC Key Laboratories of Enteric Pathogenic Microbiology, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, 210009, China. Electronic address: geyiyue@163.com. 2 Institute of Pathogenic Microbiology, NHC Key Laboratories of Enteric Pathogenic Microbiology, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, 210009, China. 3 Department of Geriatric Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China. 4 Institute of Pathogenic Microbiology, NHC Key Laboratories of Enteric Pathogenic Microbiology, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, 210009, China. Electronic address: lbcui@jscdc.cn.
[h=3]Abstract[/h] 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.
Copyright ? 2019 Elsevier Inc. All rights reserved.
[h=4]KEYWORDS:[/h] Evolution; H7N9; Influenza virus; Mutation; Neuraminidase; Peramivir; Quasispecies; Selective pressure
PMID: 31400550 DOI: 10.1016/j.virol.2019.08.004
[h=1]The evolution and characterization of influenza A(H7N9) virus under the selective pressure of peramivir.[/h] Ge Y[SUP]1[/SUP], Chi Y[SUP]2[/SUP], Min X[SUP]3[/SUP], Zhao K[SUP]2[/SUP], Wu B[SUP]2[/SUP], Wu T[SUP]2[/SUP], Zhu X[SUP]2[/SUP], Shi Z[SUP]2[/SUP], Zhu F[SUP]2[/SUP], Cui L[SUP]4[/SUP].
[h=3]Author information[/h] 1 Institute of Pathogenic Microbiology, NHC Key Laboratories of Enteric Pathogenic Microbiology, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, 210009, China. Electronic address: geyiyue@163.com. 2 Institute of Pathogenic Microbiology, NHC Key Laboratories of Enteric Pathogenic Microbiology, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, 210009, China. 3 Department of Geriatric Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China. 4 Institute of Pathogenic Microbiology, NHC Key Laboratories of Enteric Pathogenic Microbiology, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, 210009, China. Electronic address: lbcui@jscdc.cn.
[h=3]Abstract[/h] 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.
Copyright ? 2019 Elsevier Inc. All rights reserved.
[h=4]KEYWORDS:[/h] Evolution; H7N9; Influenza virus; Mutation; Neuraminidase; Peramivir; Quasispecies; Selective pressure
PMID: 31400550 DOI: 10.1016/j.virol.2019.08.004