Detection of adamantane-resistant influenza on a microarray.
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.


METHODS
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.
Townsend
Michael B
MB
Department of Chemistry and Biochemistry, The University of Colorado at Boulder, UCB #215, Boulder, CO 80309, USA.
Smagala
James A
JA
Dawson
Erica D
ED
Deyde
Varough
V
Gubareva
Larisa
L
Klimov
Alexander I
AI
Kuchta
Robert D
RD
Rowlen
Kathy L
KL
D000218:Adamantane / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D024882:Drug Resistance, Viral / Q000235:genetics*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects / Q000235:genetics; D053122:Influenza A Virus, H3N2 Subtype / Q000187:drug effects / Q000235:genetics; D008826:Microbial Sensitivity Tests / Q000379:methods; D009154:Mutation; D016571:Neural Networks, Computer; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D014763:Viral Matrix Proteins / Q000235:genetics*; D000086082:Viroporin Proteins
D000218:Adamantane; D000998:Antiviral Agents; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins