Detection of oseltamivir-resistant influenza A (H1N1) viruses with H274Y mutation during the 2007 - 2008 influenza season in Turkey

Objective: In the beginning of the 2007-2008 influenza season in Northern Hemisphere, the frequency of influenza A (H1N1) viruses bearing a previously defined oseltamivir resistance increased dramatically. This is conferring to the amino acid exchange from histidine to tyrosine at position 274 (H274Y) in neuraminidase (NA) gene. The overall frequency of oseltamivir resistance in influenza A (H1N1) strains in Europe was reported as being 25%. Although it varied between countries, it was shown that the highest percentage was in Norway (67%), and the lowest was in Spain (2%). In this study, it was aimed to evaluate the oseltamivir resistance in influenza A H1N1 isolates from Turkey during the 2007-2008 influenza season.Method: During November 2007 – May 2008, 20 samples were randomly selected between 73 influenza A (H1N1) positive samples detected with real-time RT- PCR in National Influenza Center (NIC) of Refik Saydam National Public Health Agency (RSNPHA). To detect such resistant viruses in Turkey, an RT-PCR assay was performed targeting amino acid position at 274 in NA gene of H1N1 influenza strain to investigate the presence or absence of histidine to tyrosine mutation.The NA genes of influenza, viruses were sequenced. The presence of resistance was inferred by comparison with published sequences and known resistant mutations.Results:In our study, the histidine (H) to tyrosine (Y) substitution at position 274 (275 in N1 numbering) of the NA gene was evaluated. The change indicating resistance to oseltamivir was observed in two isolates of the total 20 influenza A (H1N1) strains (10%). The partial sequence analysis results of NA segments were submitted to the National Center for Biotechnology Information (NCBI) GenBank with accession numbers GQ369800, GQ369799, GQ369798.Conclusion: Resistance to neuraminidase inhibitors was determined by NA gene sequencing in the isolates of A/H1N1 strains taken from central and eastern parts of Turkey by monitoring the presence of H274Y oseltamivir-resistant in 2008.