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Impact of avian influenza virus H5N1 neuraminidase mutations on the activity of neuraminidase and the sensibility to neuraminidase inhibitors

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Author:
No author available
Journal Title:
NATIONAL MEDICAL JOURNAL OF CHINA
Issue:
27
DOI:
10.3760/cma.j.issn.0376-2491.2010.27.014
Key Word:
正粘病毒科;神经氨酸酶;突变;酶抑制剂;禽流感病毒H5N1;Orthomyxoviridae;Neuraminidase;Mutation;Enzyme inhibitors; Avian influenza virus H5N1

Abstract: Objective To study the impact of avian influenza virus H5N1 neuraminidase mutations I117V,I314V and I117V+I314V on the sensibility of neuraminidase inhibitors(NAIs) and the activity of neuraminidase (NA).Methods The mutations were intreduced into NA genes of virus strain A/Vietnam/1203/04 (H5N1)by site-directed mutagenesis.With the A/WSN/33 (H1N1)background,recombinant influenza viruses containing NA mutations were rescued by reverse genetics.After viral propagation in chicken embryos,fluorimetric assays were conducted to assess the sensibility to NAIs and NA activity(IC50,Km&Ki).Results Compared to the wild-type viruS VNl203.the mutation I117V decreased the susceptibility to osehamivir(17-fold increment of IC50 value,20-fold increment of Ki value)and the NA activity(23-fold increment of Km value)while there Was little impact on zanamivir sensitivity(2-fold increment of IC50 value,3-fold increment of Ki value).The mutation 1314V had no marked influence on either the NA activity or the NAIs susceptibility.Conclusion It aDpears that the NA mutations of I117V and I314V Can not cause NAIs resistanee.Oseltamivir or zanamivir may still be prescribed for anti-viral treatment.

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