Amantadine and Zanamivir Resistance of Influenza A/H3N2 Viruses Isolated in Korea, 2002/03~2003/04.
10.4167/jbv.2008.38.3.127
- Author:
Kyung Ae KIM
1
;
Joo Yeon LEE
;
Woongki KIM
;
Yeol KIM
;
Yong Keun PARK
;
Chun KANG
Author Information
1. Division of Influenza and Respiratory Viruses, National Institute of Health, Korea Center for Disease Control and Prevention, Seoul, Korea. ckang@nih.go.kr
- Publication Type:Original Article
- Keywords:
Influenza virus;
Amantadine;
Zanamivir;
Resistance
- MeSH:
Amantadine;
Influenza, Human;
Kidney;
Korea;
Neuraminidase;
Orthomyxoviridae;
Polymerase Chain Reaction;
Polymorphism, Restriction Fragment Length;
Prevalence;
Seasons;
Sequence Analysis;
Zanamivir
- From:Journal of Bacteriology and Virology
2008;38(3):127-137
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
To investigate the emergence and prevalence of antiviral resistance, we analyzed influenza A/H3N2 viruses isolated in Korea during 2002/03 to 2003/04 season by genetic and phenotypic assay. For the genetic analysis to the amantadine, an M2 protein inhibitor, the M gene was amplified by RT-PCR and regions corresponding to the amino acid at positions 27, 30, and 31 were amplified by nested PCR with size of 154 bp, 95 bp, and 153 bp fragments, respectively. A total of 3 of 31 (9.7%) viruses were found to be mutated by restriction fragment length polymorphism (RFLP) with Sca I and sequence analysis, showing the single amino acid change (Ser to Asn) at position 31. Also it was observed that their growths in Madin-Darby Canine Kidney (MDCK) cells were unaffected by amantadine (up to 1 microgram/ml) in both plaque assay and WST-1 assay, confirming that these viruses were resistant against amantadine. We also examined the resistant pattern against zanamivir, a neuraminidase inhibitor, for 15 Korean influenza A/H3N2 viruses isolated in 2002~2003 season. Sequence analysis showed that there were no genetic changes of NA genes including R292K, K274Y, R152K, and E119V which were related to resistance against the neuraminidase inhibitor. In the NA inhibition assay to zanamivir, Korean isolates were found to be sensitive, ranging from 0.17 nM to 1.77 nM in 50% inhibitory concentration (IC(50)). These results suggest that monitoring for the antiviral resistance should be intensified and maintained to provide guideline for prophylaxis and treatment of influenza in Korea.
