Detection of adamantane-resistant influenza on a microarray

J Clin Virol. 2008 Jun;42(2):117-23. doi: 10.1016/j.jcv.2007.12.019. Epub 2008 Mar 4.

Abstract

Background: Influenza A has the ability to rapidly mutate and become resistant to the commonly prescribed influenza therapeutics, thereby complicating treatment decisions.

Objective: To design a cost-effective low-density microarray for use in detection of influenza resistance to the adamantanes.

Study design: We have taken advantage of functional genomics and microarray technology to design a DNA microarray that can detect the two most common mutations in the M2 protein associated with adamantane resistance, V27A and S31N.

Results: In a blind study of 22 influenza isolates, the antiviral resistance-chip (AVR-Chip) had a success rate of 95% for detecting these mutations. Microarray data from a larger set of samples were further analyzed using an artificial neural network and resulted in a correct identification rate of 94% for influenza virus samples that had V27A and S31N mutations.

Conclusions: The AVR-Chip provided a method for rapidly screening influenza viruses for adamantane sensitivity, and the general approach could be easily extended to detect resistance to other chemotherapeutics.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adamantane / pharmacology*
  • Antiviral Agents / pharmacology*
  • Drug Resistance, Viral / genetics*
  • Humans
  • Influenza A Virus, H1N1 Subtype / drug effects
  • Influenza A Virus, H1N1 Subtype / genetics
  • Influenza A Virus, H3N2 Subtype / drug effects
  • Influenza A Virus, H3N2 Subtype / genetics
  • Microbial Sensitivity Tests / methods
  • Mutation
  • Neural Networks, Computer
  • Oligonucleotide Array Sequence Analysis / methods*
  • Viral Matrix Proteins / genetics*

Substances

  • Antiviral Agents
  • M2 protein, Influenza A virus
  • Viral Matrix Proteins
  • Adamantane