Susceptibility of influenza A(H1N1)/pdm2009, seasonal A(H3N2) and B viruses to Oseltamivir in Guangdong, China between 2009 and 2014
| Autor: | Ling-zhi Jiang, Changwen Ke, Wen-zhe Su, Xiao-yang Jiao, Sheng Wang, Ping Xiong, Shan-shan Liu, Xin Zhang |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
China Oseltamivir Science viruses 030106 microbiology Mutant Neuraminidase Antiviral Agents Article Virus Madin Darby Canine Kidney Cells Microbiology 03 medical and health sciences chemistry.chemical_compound Dogs Influenza A Virus H1N1 Subtype Drug Resistance Viral Influenza Human Animals Humans Viral rna Amino Acid Sequence Gene Binding affinities Multidisciplinary Base Sequence biology Influenza A Virus H3N2 Subtype virus diseases Influenza a Virology Influenza B virus chemistry Mutation biology.protein Medicine RNA Viral Seasons |
| Zdroj: | Scientific Reports Scientific Reports, Vol 7, Iss 1, Pp 1-11 (2017) |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-017-08282-6 |
| Popis: | Nasopharyngeal swabs were collected from patients through the influenza surveillance network of the CDC of Guangdong. All specimens between 2009 and 2014 were checked for influenza virus using MDCK cells and further subtyped. Of those collected, 542 H1N1pdm09, 230 A(H3N2)and 448 B viruses selected at random were subjected to fluorescence-based NAI assays. Viral RNA was extracted from resistant isolates, and their NA genes were amplified by RT-PCR. Alignment of nucleotides and amino acids was performed. We performed structural modelling and simulations of mutants using Modeller 9.x and AutoDock and analyzed conformations and binding affinities. All tested seasonal type B and H3N2 viruses from 2009 to 2014 remained sensitive to oseltamivir. However, there were five strains (out of 198 tested isolates acquired between June and September 2013) that were resistant to oseltamivir. Another three resistant strains were identified among isolates from March to April 2014. We found that 2013/2014 oseltamivir-resistant strains and 2012/2013/2014 oseltamivir-sensitive strains had all or some of the following mutations: N44S, N200S,V241I, I321V,N369K, N386 K and K432E. MutationsV241I, N369K, N386K and K432E, alone or in conjunction with H275Y, had a significant impact on the binding pattern and affinity of oseltamivir for neuraminidase, rendering neuraminidase less susceptible. |
| Databáze: | OpenAIRE |
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