tetano
Editor, Senior Moderator
J Virol. 2012 Feb 29. [Epub ahead of print]
Decreased neuraminidase activity is important for the adaptation of H5N1 influenza virus to human airway epithelium.
Ilyushina NA, Bovin NV, Webster RG.
Source
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105-3678, USA.
Abstract
Highly pathogenic avian H5N1 influenza viruses remain a pandemic threat. Antiviral drugs such as neuraminidase (NA) inhibitors will be crucial for disease control in the event of a pandemic. Should drug-resistant H5N1 viruses develop, all defense strategies will be compromised.To determine the likelihood and mechanisms of emergence of NA inhibitor-resistant H5N1 variants in humans, we serially passaged 2 H5N1 viruses,A/Hong Kong/213/03and A/Turkey/65-1242/06, in normal human bronchial epithelial (NHBE) cells in the presence of oseltamivir, zanamivir, or peramivir.To monitor the emergence of changes associated with the adaptation of H5N1 viruses to humans, we passaged the strainsin the absence of drugs.Under pressure of each NA inhibitor, A/Turkey/65-1242/06 developedmutations in the hemagglutinin (HA) (H28R, P194L/T215I) and NA (E119A) proteins that reduced virus binding to α2,3sialyl receptor and NA activity. Oseltamivir pressureselected a variant of A/Hong Kong/213/03 virus with HA P194S mutation that decreased viral binding to α2,6 receptor.Under peramivir pressure, A/Hong Kong/213/03 virus developed a novel NAmutation,R156K, thatreduced binding to all 3drugs,about 90% loss of NA activity, and compromised replication in NHBE cells. Both strains were eliminated in NHBE cells when they were cultivated in the absence of drugs.Here we show for the first time that decreased NA activity mediated through NA inhibitors is essential for the adaptation of pandemic H5N1 influenza to humans.This ability of decreased NA activity to promote H5N1 infection underlines the necessity to optimize management strategies for a plausible H5N1 pandemic.
PMID:
22379077
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22379077
Decreased neuraminidase activity is important for the adaptation of H5N1 influenza virus to human airway epithelium.
Ilyushina NA, Bovin NV, Webster RG.
Source
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105-3678, USA.
Abstract
Highly pathogenic avian H5N1 influenza viruses remain a pandemic threat. Antiviral drugs such as neuraminidase (NA) inhibitors will be crucial for disease control in the event of a pandemic. Should drug-resistant H5N1 viruses develop, all defense strategies will be compromised.To determine the likelihood and mechanisms of emergence of NA inhibitor-resistant H5N1 variants in humans, we serially passaged 2 H5N1 viruses,A/Hong Kong/213/03and A/Turkey/65-1242/06, in normal human bronchial epithelial (NHBE) cells in the presence of oseltamivir, zanamivir, or peramivir.To monitor the emergence of changes associated with the adaptation of H5N1 viruses to humans, we passaged the strainsin the absence of drugs.Under pressure of each NA inhibitor, A/Turkey/65-1242/06 developedmutations in the hemagglutinin (HA) (H28R, P194L/T215I) and NA (E119A) proteins that reduced virus binding to α2,3sialyl receptor and NA activity. Oseltamivir pressureselected a variant of A/Hong Kong/213/03 virus with HA P194S mutation that decreased viral binding to α2,6 receptor.Under peramivir pressure, A/Hong Kong/213/03 virus developed a novel NAmutation,R156K, thatreduced binding to all 3drugs,about 90% loss of NA activity, and compromised replication in NHBE cells. Both strains were eliminated in NHBE cells when they were cultivated in the absence of drugs.Here we show for the first time that decreased NA activity mediated through NA inhibitors is essential for the adaptation of pandemic H5N1 influenza to humans.This ability of decreased NA activity to promote H5N1 infection underlines the necessity to optimize management strategies for a plausible H5N1 pandemic.
PMID:
22379077
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22379077