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Zanamivir-resistant influenza viruses with a novel neuraminidase mutation.
J Virol 2009; 83(20):10366-73JV

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.

Authors+Show Affiliations

WHO Collaborating Centre for Reference and Research on Influenza, 10 Wreckyn St., North Melbourne, Victoria 3051, Australia. aeron.hurt@influenzacentre.orgNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19641000

Citation

Hurt, Aeron C., et al. "Zanamivir-resistant Influenza Viruses With a Novel Neuraminidase Mutation." Journal of Virology, vol. 83, no. 20, 2009, pp. 10366-73.
Hurt AC, Holien JK, Parker M, et al. Zanamivir-resistant influenza viruses with a novel neuraminidase mutation. J Virol. 2009;83(20):10366-73.
Hurt, A. C., Holien, J. K., Parker, M., Kelso, A., & Barr, I. G. (2009). Zanamivir-resistant influenza viruses with a novel neuraminidase mutation. Journal of Virology, 83(20), pp. 10366-73. doi:10.1128/JVI.01200-09.
Hurt AC, et al. Zanamivir-resistant Influenza Viruses With a Novel Neuraminidase Mutation. J Virol. 2009;83(20):10366-73. PubMed PMID: 19641000.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Zanamivir-resistant influenza viruses with a novel neuraminidase mutation. AU - Hurt,Aeron C, AU - Holien,Jessica K, AU - Parker,Michael, AU - Kelso,Anne, AU - Barr,Ian G, Y1 - 2009/07/29/ PY - 2009/7/31/entrez PY - 2009/7/31/pubmed PY - 2009/10/17/medline SP - 10366 EP - 73 JF - Journal of virology JO - J. Virol. VL - 83 IS - 20 N2 - 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. SN - 1098-5514 UR - https://www.unboundmedicine.com/medline/citation/19641000/Zanamivir_resistant_influenza_viruses_with_a_novel_neuraminidase_mutation_ L2 - http://jvi.asm.org/cgi/pmidlookup?view=long&pmid=19641000 DB - PRIME DP - Unbound Medicine ER -