title: Drug susceptibility of influenza A/H3N2 strains co-circulating during 2009 influenza pandemic: first report from Mumbai.
abstract: OBJECTIVE
  From its first instance in 1977, resistance to amantadine, a matrix (M2) inhibitor has been increasing among influenza A/H3N2, thus propelling the use of oseltamivir, a neuraminidase (NA) inhibitor as a next line drug. Information on drug susceptibility to amantadine and neuraminidase inhibitors for influenza A/H3N2 viruses in India is limited with no published data from Mumbai. This study aimed at examining the sensitivity to M2 and NA inhibitors of influenza A/H3N2 strains isolated from 2009 to 2011 in Mumbai.
  
  
  METHODS
  Nasopharyngeal swabs positive for influenza A/H3N2 virus were inoculated on Madin-Darby canine kidney (MDCK) cell line for virus isolation. Molecular analysis of NA and M2 genes was used to detect known mutations contributing to resistance. Resistance to neuraminidase was assayed using a commercially available chemiluminescence based NA-Star assay kit.
  
  
  RESULTS
  Genotypically, all isolates were observed to harbor mutations known to confer resistance to amantadine. However, no know mutations conferring resistance to NA inhibitors were detected. The mean IC50 value for oseltamivir was 0.25 nM. One strain with reduced susceptibility to the neuraminidase inhibitor (IC₅₀=4.08 nM) was isolated from a patient who had received oseltamivir treatment. Phylogenetic analysis postulate the emergence of amantadine resistance in Mumbai may be due to genetic reassortment with the strains circulating in Asia and North America.
  
  
  CONCLUSIONS
  Surveillance of drug susceptibility helped us to identify an isolate with reduced sensitivity to oseltamivir. Therefore, we infer that such surveillance would help in understanding possible trends underlying the emergence of resistant variants in humans.
authors.affiliation: Department of Virology and Immunology, Haffkine Institute for Training, Research and Testing, Parel, Mumbai, Maharashtra, India. Electronic address: devanshi.gohil@gmail.com.
authors.forename: Devanshi J
authors.initials: DJ
authors.lastname: Gohil
authors.affiliation: Department of Virology and Immunology, Haffkine Institute for Training, Research and Testing, Parel, Mumbai, Maharashtra, India.
authors.forename: Sweta T
authors.initials: ST
authors.lastname: Kothari
authors.affiliation: Department of Bioinformatics, Guru Nanak Khalsa College, Mumbai, Maharashtra, India.
authors.forename: Pramod S
authors.initials: PS
authors.lastname: Shinde
authors.affiliation: Principal K.M. Kundnani College of Pharmacy, Mumbai, Maharashtra, India.
authors.forename: Anand S
authors.initials: AS
authors.lastname: Chintakrindi
authors.affiliation: Molecular Biology and Virology, HiMedia Laboratories, Mumbai, Maharashtra, India.
authors.forename: Rhuta
authors.initials: R
authors.lastname: Meharunkar
authors.affiliation: Department of Virology and Immunology, Haffkine Institute for Training, Research and Testing, Parel, Mumbai, Maharashtra, India; Molecular Biology and Virology, HiMedia Laboratories, Mumbai, Maharashtra, India.
authors.forename: Rajas V
authors.initials: RV
authors.lastname: Warke
authors.affiliation: Principal K.M. Kundnani College of Pharmacy, Mumbai, Maharashtra, India.
authors.forename: Meena A
authors.initials: MA
authors.lastname: Kanyalkar
authors.affiliation: Department of Virology and Immunology, Haffkine Institute for Training, Research and Testing, Parel, Mumbai, Maharashtra, India.
authors.forename: Abhay S
authors.initials: AS
authors.lastname: Chowdhary
authors.affiliation: Department of Virology and Immunology, Haffkine Institute for Training, Research and Testing, Parel, Mumbai, Maharashtra, India.
authors.forename: Ranjana A
authors.initials: RA
authors.lastname: Deshmukh
mesh_terms: D000547:Amantadine / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D004285:Dogs; D024882:Drug Resistance, Viral / Q000187:drug effects; D006801:Humans; D007194:India; D053122:Influenza A Virus, H3N2 Subtype / Q000187:drug effects* / Q000235:genetics; D007251:Influenza, Human / Q000821:virology*; D061985:Madin Darby Canine Kidney Cells; D009154:Mutation; D009305:Nasopharynx / Q000821:virology*; D009439:Neuraminidase / Q000378:metabolism; D053139:Oseltamivir / Q000031:analogs & derivatives* / Q000494:pharmacology; D058873:Pandemics; D010802:Phylogeny; D014763:Viral Matrix Proteins / Q000235:genetics; D000086082:Viroporin Proteins
chemical_list: D000547:Amantadine; D000998:Antiviral Agents; D009439:Neuraminidase; D053139:Oseltamivir; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins; C535162:oseltamivir carboxylate
keywords: Amantadine; Influenza; Mumbai; Oseltamivir; Phylogenetic analysis; Surveillance