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Zanamivir-resistant influenza viruses with a novel neuraminidase mutation.
- Source :
-
Journal of virology [J Virol] 2009 Oct; Vol. 83 (20), pp. 10366-73. Date of Electronic Publication: 2009 Jul 29. - Publication Year :
- 2009
-
Abstract
- The neuraminidase inhibitors zanamivir and oseltamivir are marketed for the treatment and prophylaxis of influenza and have been stockpiled by many countries for use in a pandemic. Although recent surveillance has identified a striking increase in the frequency of oseltamivir-resistant seasonal influenza A (H1N1) viruses in Europe, the United States, Oceania, and South Africa, to date there have been no reports of significant zanamivir resistance among influenza A (H1N1) viruses or any other human influenza viruses. We investigated the frequency of oseltamivir and zanamivir resistance in circulating seasonal influenza A (H1N1) viruses in Australasia and Southeast Asia. Analysis of 391 influenza A (H1N1) viruses isolated between 2006 and early 2008 from Australasia and Southeast Asia revealed nine viruses (2.3%) that demonstrated markedly reduced zanamivir susceptibility and contained a previously undescribed Gln136Lys (Q136K) neuraminidase mutation. The mutation had no effect on oseltamivir susceptibility but caused approximately a 300-fold and a 70-fold reduction in zanamivir and peramivir susceptibility, respectively. The role of the Q136K mutation in conferring zanamivir resistance was confirmed using reverse genetics. Interestingly, the mutation was not detected in the primary clinical specimens from which these mutant isolates were grown, suggesting that the resistant viruses either occurred in very low proportions in the primary clinical specimens or arose during MDCK cell culture passage. Compared to susceptible influenza A (H1N1) viruses, the Q136K mutant strains displayed greater viral fitness than the wild-type virus in MDCK cells but equivalent infectivity and transmissibility in a ferret model.
- Subjects :
- Animals
Asia, Southeastern
Australasia
Cell Line
Female
Ferrets virology
Humans
Influenza A Virus, H1N1 Subtype enzymology
Influenza A Virus, H1N1 Subtype genetics
Influenza A Virus, H1N1 Subtype pathogenicity
Influenza, Human virology
Microbial Sensitivity Tests methods
Neuraminidase genetics
Orthomyxoviridae Infections virology
Antiviral Agents pharmacology
Drug Resistance, Viral genetics
Influenza A Virus, H1N1 Subtype drug effects
Mutation
Neuraminidase antagonists & inhibitors
Oseltamivir pharmacology
Zanamivir pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5514
- Volume :
- 83
- Issue :
- 20
- Database :
- MEDLINE
- Journal :
- Journal of virology
- Publication Type :
- Academic Journal
- Accession number :
- 19641000
- Full Text :
- https://doi.org/10.1128/JVI.01200-09