Identification of oseltamivir resistance among pandemic and seasonal influenza A (H1N1) viruses by an His275Tyr genotyping assay using the cycling probe method

J Clin Microbiol. 2011 Jan;49(1):125-30. doi: 10.1128/JCM.01401-10. Epub 2010 Nov 17.

Abstract

Neuraminidase inhibitors are agents used against influenza viruses; however, the emergence of drug-resistant strains is a major concern. Recently, the prevalence of oseltamivir-resistant seasonal influenza A (H1N1) virus increased globally and the emergence of oseltamivir-resistant pandemic influenza A (H1N1) 2009 viruses was reported. In this study, we developed a cycling probe real-time PCR method for the detection of oseltamivir-resistant seasonal influenza A (H1N1) and pandemic influenza A (H1N1) 2009 viruses. We designed two sets of primers and probes that were labeled with 6-carboxyfluorescein or 6-carboxy-X-rhodamine to identify single nucleotide polymorphisms (SNPs) that correspond to a histidine and a tyrosine at position 275 in the neuraminidase protein, respectively. These SNPs confer susceptibility and resistance to oseltamivir, respectively. In the 2007-2008 season, the prevalence of oseltamivir-resistant H1N1 viruses was 0% (0/72), but in the 2008-2009 season, it increased to 100% (282/282). In the 2009-2010 season, all of the pandemic influenza A (H1N1) 2009 viruses were susceptible to oseltamivir (0/73, 0%). This method is sensitive and specific for the screening of oseltamivir-resistant influenza A (H1N1) viruses. This method is applicable to routine laboratory-based monitoring of drug resistance and patient management during antiviral therapy.

Publication types

  • Evaluation Study

MeSH terms

  • Amino Acid Substitution / genetics*
  • Antiviral Agents / pharmacology*
  • Genotype
  • Humans
  • Influenza A Virus, H1N1 Subtype / drug effects*
  • Influenza A Virus, H1N1 Subtype / genetics
  • Influenza, Human / virology*
  • Microbial Sensitivity Tests / methods
  • Molecular Typing / methods*
  • Neuraminidase / genetics*
  • Oseltamivir / pharmacology*
  • Polymorphism, Single Nucleotide
  • Sensitivity and Specificity
  • Viral Proteins / genetics*

Substances

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