tetano
Editor, Senior Moderator
J Virol. 2016 Feb 24. pii: JVI.00013-16. [Epub ahead of print]
[h=1]Neuraminidase Activity and The Resistance of 2009 Pandemic H1N1 Influenza Virus to Antiviral Activity in Bronchoalveolar Fluid.[/h] Ruangrung K[SUP]1[/SUP], Suptawiwat O[SUP]1[/SUP], Maneechotesuwan K[SUP]2[/SUP], Boonarkart C[SUP]1[/SUP], Chakritbudsabong W[SUP]3[/SUP], Assawabhumi J[SUP]2[/SUP], Bhattarakosol P[SUP]4[/SUP], Uiprasertkul M[SUP]5[/SUP], Puthavathana P[SUP]6[/SUP], Wiriyarat W[SUP]3[/SUP], Jongkaewwattana A[SUP]7[/SUP], Auewarakul P[SUP]8[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Human bronchoalveolar fluid is known to have anti-influenza activity. It is believed to be a frontline innate defense against the virus. Several anti-viral factors, including surfactant protein D, are believed to contribute to the activity. The 2009 pandemic H1N1 influenza was previously shown to be less sensitive to surfactant protein D. Nevertheless, whether different influenza strains have different sensitivity to the overall anti-influenza activity of human bronchoalveolar fluid was not known. We compared the sensitivity of 2009 pandemic H1N1, seasonal H1N1, and seasonal H3N2 influenza strains to an inhibition by human bronchoalveolar lavage (BAL). The pandemic and seasonal H1N1 strains showed lower sensitivity to human BAL than the H3N2 strains. The BAL anti-influenza activity could be enhanced by Oseltamivir, indicating that the viral neuraminidase (NA) activity could provide a resistance to the anti-viral defense. In accordance with this finding, the BAL anti-influenza activity was found to be sensitive to sialidase. The Oseltamivir-resistant mutation, H275Y, rendered the pandemic H1N1 virus but not the seasonal H1N1 virus more sensitive to BAL. Since only the seasonal H1N1 but not the pandemic H1N1 had compensatory mutations that allowed Oseltamivir-resistant strains to maintain NA enzymatic activity and transmission fitness, the resistance to BAL of the drug resistant seasonal H1N1 virus might play a role in the viral fitness.
[h=4]IMPORTANCE:[/h] Human airway secretion contains anti-influenza activity. Different influenza strains may vary in their susceptibility to this antiviral activity. Here we show that the 2009 pandemic and seasonal H1N1 influenza viruses were less sensitive to human bronchoalveolar lavage than H3N2 seasonal influenza virus. The resistance to the pulmonary innate antiviral activity of the pandemic virus was determined by its NA gene and that the NA inhibitor resistant mutation, H275Y, abolished this resistance of the pandemic H1N1 but not the seasonal H1N1 virus, which had compensatory mutations that maintained the fitness of drug resistant strains. Therefore, the innate respiratory tract defense may be a barrier against NA inhibitor resistant mutants and evasion of this defense may play a role in emergence and spreading of drug resistant strains.
Copyright ? 2016, American Society for Microbiology. All Rights Reserved.
PMID: 26912622 [PubMed - as supplied by publisher]
[h=1]Neuraminidase Activity and The Resistance of 2009 Pandemic H1N1 Influenza Virus to Antiviral Activity in Bronchoalveolar Fluid.[/h] Ruangrung K[SUP]1[/SUP], Suptawiwat O[SUP]1[/SUP], Maneechotesuwan K[SUP]2[/SUP], Boonarkart C[SUP]1[/SUP], Chakritbudsabong W[SUP]3[/SUP], Assawabhumi J[SUP]2[/SUP], Bhattarakosol P[SUP]4[/SUP], Uiprasertkul M[SUP]5[/SUP], Puthavathana P[SUP]6[/SUP], Wiriyarat W[SUP]3[/SUP], Jongkaewwattana A[SUP]7[/SUP], Auewarakul P[SUP]8[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Human bronchoalveolar fluid is known to have anti-influenza activity. It is believed to be a frontline innate defense against the virus. Several anti-viral factors, including surfactant protein D, are believed to contribute to the activity. The 2009 pandemic H1N1 influenza was previously shown to be less sensitive to surfactant protein D. Nevertheless, whether different influenza strains have different sensitivity to the overall anti-influenza activity of human bronchoalveolar fluid was not known. We compared the sensitivity of 2009 pandemic H1N1, seasonal H1N1, and seasonal H3N2 influenza strains to an inhibition by human bronchoalveolar lavage (BAL). The pandemic and seasonal H1N1 strains showed lower sensitivity to human BAL than the H3N2 strains. The BAL anti-influenza activity could be enhanced by Oseltamivir, indicating that the viral neuraminidase (NA) activity could provide a resistance to the anti-viral defense. In accordance with this finding, the BAL anti-influenza activity was found to be sensitive to sialidase. The Oseltamivir-resistant mutation, H275Y, rendered the pandemic H1N1 virus but not the seasonal H1N1 virus more sensitive to BAL. Since only the seasonal H1N1 but not the pandemic H1N1 had compensatory mutations that allowed Oseltamivir-resistant strains to maintain NA enzymatic activity and transmission fitness, the resistance to BAL of the drug resistant seasonal H1N1 virus might play a role in the viral fitness.
[h=4]IMPORTANCE:[/h] Human airway secretion contains anti-influenza activity. Different influenza strains may vary in their susceptibility to this antiviral activity. Here we show that the 2009 pandemic and seasonal H1N1 influenza viruses were less sensitive to human bronchoalveolar lavage than H3N2 seasonal influenza virus. The resistance to the pulmonary innate antiviral activity of the pandemic virus was determined by its NA gene and that the NA inhibitor resistant mutation, H275Y, abolished this resistance of the pandemic H1N1 but not the seasonal H1N1 virus, which had compensatory mutations that maintained the fitness of drug resistant strains. Therefore, the innate respiratory tract defense may be a barrier against NA inhibitor resistant mutants and evasion of this defense may play a role in emergence and spreading of drug resistant strains.
Copyright ? 2016, American Society for Microbiology. All Rights Reserved.
PMID: 26912622 [PubMed - as supplied by publisher]