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KMID : 1120220130040060323
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Osong Public Health and Research Perspectives
2013 Volume.4 No. 6 p.323 ~ p.328
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Generation and Characterization of Recombinant Influenza A(H1N1) Viruses Resistant to Neuraminidase Inhibitors
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Choi Woo-Young
Shin Jin-Young
Jeong Hwan-Eui
Jeong Mi-Jin
Kim Su-Jin
Lee Joo-Yeon
Kang Chun
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Abstract
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Objectives: To examine the effect of neuraminidase (NA) mutations on the NA inhibitor (NAI) resistance phenotype, the recombinant influenza A/Chungbuk/4448/2008(H1N1) virus isolated in South Korea during the 2008?2009 season was generated by reverse genetics.
Methods: Site-directed mutagenesis was introduced on the NA gene of A/Chungbuk/4448/2008(H1N1) virus, and a total of 23 single, double, and triple mutants were generated. Resistance phenotype of these recombinant viruses was determined by NA-inhibition (NAI) assays based on a fluorometric method using two NAIs (oseltamivir and zanamivir).
Results: NA-inhibition assays showed that all the single and double mutants containing the Y275 except the single Y275-E119V mutant conferred important levels of resistance to oseltamivir, whereas all the single, double, and triple mutants containing the E119V mutation were associated with the resistance to zanamivir.
Conclusion: Considering the effect of mutations in NA gene on the resistance to NAIs, it is important to monitor the possible emergence and dissemination of multidrug-resistant variants in the human population due to amino acid changes at NA gene as well as to develop novel NAIs.
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KEYWORD
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influenza virus, neuraminidase inhibitors, recombinant drug-resistant virus, reverse genetics
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