[Impact of avian influenza virus H5N1 neuraminidase mutations on the activity of neuraminidase and the sensibility to neuraminidase inhibitors].
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 introduced 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 (IC(50), Km & Ki).


RESULTS
Compared to the wild-type virus VN1203, the mutation I117V decreased the susceptibility to oseltamivir (17-fold increment of IC(50) 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 IC(50) value, 3-fold increment of Ki value). The mutation I314V had no marked influence on either the NA activity or the NAIs susceptibility.


CONCLUSIONS
It appears that the NA mutations of I117V and I314V can not cause NAIs resistance. Oseltamivir or zanamivir may still be prescribed for anti-viral treatment.
Chen
Zi
Z
Department of Infectious Diseases, Second Xiangya Hospital, Central South University, Changsha 410011, China.
Zheng
Yu-huang
YH
Lin
Yipu
Y
Collins
Patrick J
PJ
Hay
Alan J
AJ
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D002642:Chick Embryo / Q000821:virology; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects / Q000235:genetics; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects* / Q000235:genetics; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D009439:Neuraminidase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D053139:Oseltamivir / Q000494:pharmacology; D053243:Zanamivir / Q000494:pharmacology
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D053139:Oseltamivir; D009439:Neuraminidase; D053243:Zanamivir