کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
3369658 | 1219046 | 2008 | 5 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Impact of influenza A virus neuraminidase mutations on the stability, activity, and sensibility of the neuraminidase to neuraminidase inhibitors Impact of influenza A virus neuraminidase mutations on the stability, activity, and sensibility of the neuraminidase to neuraminidase inhibitors](/preview/png/3369658.png)
BackgroundThe influenza neuraminidase plays a critical role in the spread of the influenza A and B viruses. Through the cleavage of terminal sialic acid from glycoconjugates, it facilitates the elution of progeny virions from infected cells and prevents their self-aggregation.ObjectivesOur objective was to study the impact of mutations at framework sites not under direct selective pressure in the neuraminidase active site.Study designIn the A/Moscow/10/99 (H3N2) virus background, viruses containing mutations in NA framework residues (E119D, R156K, W178L, S179A, D198N, I222L, E227G, H274Y, E277G, N294D, and E425G) were constructed by reverse genetics. After several passages on MDCK cells, fluorimetric assays were conducted to assess the neuraminidase activity and sensibility to the neuraminidase inhibitors (IC50).ResultsAmong the viruses detectable through the phenotypic tests, R156K, I222L, H274Y, N294D and E425G viruses presented a NA activity between 70% and 100% of the A/Moscow/10/99 wild type one. The D198N and the E119D mutations decreased seriously in NA activity compared to the wild-type (>10-fold). The I222L mutation reduced susceptibility to oseltamivir (18-fold).ConclusionWith the exception of one mutation, framework mutations on N2 background do not induce resistance. Nevertheless they tend to decrease slowly the sensitivity to one or the other inhibitors.
Journal: Journal of Clinical Virology - Volume 41, Issue 1, January 2008, Pages 20–24