Surveillance and oseltamivir resistance of human influenza a virus in Turkey during the 2007-2008 season

J Med Virol. 2009 Sep;81(9):1645-51. doi: 10.1002/jmv.21546.

Abstract

Monitoring the activity of influenza viruses is important for establishing the circulating types and for detection of the emergence of novel sub-types and antiviral resistant strains. This is the first report from Turkey on the surveillance and oseltamivir resistance of influenza viruses in 2007-2008. Five hundred twenty-four nasal swabs were tested from different geographical regions in Turkey during November 2007-April 2008. One hundred sixty-three (31%) samples were positive for influenza viruses of which 111 (68%) were influenza A, 52 (31%) influenza B using an immuno-capture ELISA. Forty isolates were selected at random from influenza A positive samples and grown in MDCK cell cultures. The supernatant of the cell cultures was used for RNA extraction followed by RT-PCR to detect the sub-types. Sub-typing revealed all samples as A/H1N1. The N1 gene segment of 30 A/H1N1 samples was sequenced in part, from the 201st to 365th residue, which included the critical region for oseltamivir resistance. Then resulting sequences were analyzed with oseltamivir sensitive and resistant strains obtained from National Center for Biotechnology Information (NCBI) GenBank by CLC Main Workbench Software. H275Y (H274Y according to N2 numbering) mutation, which is known to confer resistance to oseltamivir, was detected in 6 out of 30 (20%) H1N1 isolates from four cities (Istanbul, Bursa, Ankara, and Izmir). The D354G mutation was observed in all oseltamivir resistant H1N1 isolates but not in the oseltamivir sensitive isolates. Assay of neuraminidase activity revealed that these isolates were resistant to oseltamivir, but sensitive to zanamivir.

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution / genetics*
  • Animals
  • Antiviral Agents / pharmacology*
  • Cities
  • Cluster Analysis
  • Drug Resistance, Viral*
  • Enzyme-Linked Immunosorbent Assay / methods
  • Humans
  • Influenza A Virus, H1N1 Subtype / drug effects*
  • Influenza A Virus, H1N1 Subtype / isolation & purification
  • Influenza B virus / isolation & purification
  • Influenza, Human / virology*
  • Molecular Sequence Data
  • Mutation, Missense
  • Nasal Mucosa / virology
  • Neuraminidase / genetics
  • Oseltamivir / pharmacology*
  • Phylogeny
  • RNA, Viral / genetics
  • Sequence Analysis, DNA
  • Sequence Homology
  • Turkey
  • Viral Proteins / genetics

Substances

  • Antiviral Agents
  • RNA, Viral
  • Viral Proteins
  • Oseltamivir
  • NA protein, influenza A virus
  • Neuraminidase

Associated data

  • GENBANK/EU681262
  • GENBANK/EU681263
  • GENBANK/EU681264
  • GENBANK/EU681265
  • GENBANK/EU681266