title: Molecular surveillance of antiviral drug resistance of influenza A/H3N2 virus in Singapore, 2009-2013.
abstract: Adamantanes and neuraminidase inhibitors (NAIs) are two classes of antiviral drugs available for the chemoprophylaxis and treatment of influenza infections. To determine the frequency of drug resistance in influenza A/H3N2 viruses in Singapore, large-scale sequencing of neuraminidase (NA) and matrix protein (MP) genes was performed directly without initial culture amplification. 241 laboratory-confirmed influenza A/H3N2 clinical samples, collected between May 2009 and November 2013 were included. In total, 229 NA (95%) and 241 MP (100%) complete sequences were obtained. Drug resistance mutations in the NA and MP genes were interpreted according to published studies. For the NAIs, a visual inspection of the aligned NA sequences revealed no known drug resistant genotypes (DRGs). For the adamantanes, the well-recognised S31N DRG was identified in all 241 MP genes. In addition, there was an increasing number of viruses carrying the combination of D93G+Y155F+D251V (since May 2013) or D93G (since March 2011) mutations in the NA gene. However, in-vitro NAI testing indicated that neither D93G+Y155F+D251V nor D93G alone conferred any changes in NAI susceptibility. Lastly, an I222T mutation in the NA gene that has previously been reported to cause oseltamivir-resistance in influenza A/H1N1/2009, B, and A/H5N1, was detected from a treatment-naïve patient. Further in-vitro NAI testing is required to confirm the effect of this mutation in A/H3N2 virus.
authors: Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Laboratory Medicine, National University Hospital, National University Health System, Singapore, Singapore.
authors: Hong Kai
authors: HK
authors: Lee
authors: Clinical Microbiology, Leicester Royal Infirmary, Leicester, United Kingdom.
authors: Julian Wei-Tze
authors: JW
authors: Tang
authors: Department of Laboratory Medicine, National University Hospital, National University Health System, Singapore, Singapore.
authors: Tze Ping
authors: TP
authors: Loh
authors: WHO Collaborating Centre for Reference and Research on Influenza, Melbourne, VIC, Australia; Melbourne School of Population and Global Health, University of Melbourne, VIC, Australia.
authors: Aeron C
authors: AC
authors: Hurt
authors: Department of Pathology, Singapore General Hospital, Singapore, Singapore.
authors: Lynette Lin-Ean
authors: LL
authors: Oon
authors: Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Laboratory Medicine, National University Hospital, National University Health System, Singapore, Singapore.
authors: Evelyn Siew-Chuan
authors: ES
authors: Koay
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D024882:Drug Resistance, Viral / Q000235:genetics*; D005814:Genes, Viral; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics*; D007251:Influenza, Human / Q000453:epidemiology / Q000821:virology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009439:Neuraminidase / Q000737:chemistry / Q000235:genetics; D010802:Phylogeny; D012846:Singapore; D014763:Viral Matrix Proteins / Q000235:genetics
chemical_list: D014763:Viral Matrix Proteins; D009439:Neuraminidase
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