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Article: The R292K Mutation That Confers Resistance to Neuraminidase Inhibitors Leads to Competitive Fitness Loss of A/Shanghai/1/2013(H7N9) Influenza Virus in Ferrets.

TitleThe R292K Mutation That Confers Resistance to Neuraminidase Inhibitors Leads to Competitive Fitness Loss of A/Shanghai/1/2013(H7N9) Influenza Virus in Ferrets.
Authors
Issue Date2014
PublisherOxford University Press. The Journal's web site is located at http://www.oxfordjournals.org/our_journals/jid/
Citation
Journal of Infectious Diseases, 2014, v. 210 n. 12, p. 1900-1908 How to Cite?
AbstractBACKGROUND: Neuraminidase (NA) inhibitors are the only licensed therapeutic option for human zoonotic H7N9 infections. An NA-R292K mutation that confers broad-spectrum resistance to NA inhibitors has been documented in H7N9 patients after treatment. METHODS: We evaluated the transmission potential of a human influenza A H7N9 isolate with a NA-R292K mutation in the ferret model followed by genotyping assay to monitor its competitive fitness in vivo. RESULTS: Plaque-purified A/Shanghai/1/2013 wild-type and NA-R292K viruses transmitted at comparable efficiency to direct or respiratory droplet contact ferrets. In ferrets inoculated with the plaque-purified A/Shanghai/1/2013 NA-R292K virus with dominant K292 (94%), the resistant K292 genotype was outgrown by the wild-type R292 genotype during the course of infection. Transmission of the resistant K292 genotype was detected in 3/4 direct contact and 3/4 respiratory droplet contact ferrets at early time points but was gradually replaced by the wild-type genotype. In the respiratory tissues of inoculated or infected ferrets, the wild-type R292 genotype dominated in the nasal turbinate, whereas the resistant K292 genotype was more frequently detected in the lungs. CONCLUSIONS: The NA inhibitor-resistant H7N9 virus with the NA-R292K mutation may transmit among ferrets but showed compromised fitness in vivo while in competition with the wild-type virus.
Persistent Identifierhttp://hdl.handle.net/10722/202042
ISSN
2015 Impact Factor: 6.344
2015 SCImago Journal Rankings: 4.000
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorYen, HY-
dc.contributor.authorZhou, J-
dc.contributor.authorChoy, KT-
dc.contributor.authorSia, SF-
dc.contributor.authorTeng, O-
dc.contributor.authorNg, IHY-
dc.contributor.authorFang, VJ-
dc.contributor.authorHu, Y-
dc.contributor.authorWang, W-
dc.contributor.authorCowling, BJ-
dc.contributor.authorNicholls, JM-
dc.contributor.authorGuan, Y-
dc.contributor.authorPeiris, JSM-
dc.date.accessioned2014-08-21T07:59:36Z-
dc.date.available2014-08-21T07:59:36Z-
dc.date.issued2014-
dc.identifier.citationJournal of Infectious Diseases, 2014, v. 210 n. 12, p. 1900-1908-
dc.identifier.issn0022-1899-
dc.identifier.urihttp://hdl.handle.net/10722/202042-
dc.description.abstractBACKGROUND: Neuraminidase (NA) inhibitors are the only licensed therapeutic option for human zoonotic H7N9 infections. An NA-R292K mutation that confers broad-spectrum resistance to NA inhibitors has been documented in H7N9 patients after treatment. METHODS: We evaluated the transmission potential of a human influenza A H7N9 isolate with a NA-R292K mutation in the ferret model followed by genotyping assay to monitor its competitive fitness in vivo. RESULTS: Plaque-purified A/Shanghai/1/2013 wild-type and NA-R292K viruses transmitted at comparable efficiency to direct or respiratory droplet contact ferrets. In ferrets inoculated with the plaque-purified A/Shanghai/1/2013 NA-R292K virus with dominant K292 (94%), the resistant K292 genotype was outgrown by the wild-type R292 genotype during the course of infection. Transmission of the resistant K292 genotype was detected in 3/4 direct contact and 3/4 respiratory droplet contact ferrets at early time points but was gradually replaced by the wild-type genotype. In the respiratory tissues of inoculated or infected ferrets, the wild-type R292 genotype dominated in the nasal turbinate, whereas the resistant K292 genotype was more frequently detected in the lungs. CONCLUSIONS: The NA inhibitor-resistant H7N9 virus with the NA-R292K mutation may transmit among ferrets but showed compromised fitness in vivo while in competition with the wild-type virus.-
dc.languageeng-
dc.publisherOxford University Press. The Journal's web site is located at http://www.oxfordjournals.org/our_journals/jid/-
dc.relation.ispartofJournal of Infectious Diseases-
dc.titleThe R292K Mutation That Confers Resistance to Neuraminidase Inhibitors Leads to Competitive Fitness Loss of A/Shanghai/1/2013(H7N9) Influenza Virus in Ferrets.-
dc.typeArticle-
dc.identifier.emailYen, HY: hyen@hku.hk-
dc.identifier.emailChoy, KT: ktchoy@hku.hk-
dc.identifier.emailSia, SF: sfsia@hkucc.hku.hk-
dc.identifier.emailNg, IHY: ihyng@hkucc.hku.hk-
dc.identifier.emailFang, VJ: vickyf@hku.hk-
dc.identifier.emailCowling, BJ: bcowling@hku.hk-
dc.identifier.emailNicholls, JM: jmnichol@hkucc.hku.hk-
dc.identifier.emailGuan, Y: yguan@hkucc.hku.hk-
dc.identifier.emailPeiris, JSM: malik@hkucc.hku.hk-
dc.identifier.authorityYen, HY=rp00304-
dc.identifier.authorityCowling, BJ=rp01326-
dc.identifier.authorityNicholls, JM=rp00364-
dc.identifier.authorityGuan, Y=rp00397-
dc.identifier.authorityPeiris, JSM=rp00410-
dc.identifier.doi10.1093/infdis/jiu353-
dc.identifier.pmid24951824-
dc.identifier.pmcidPMC4296180-
dc.identifier.hkuros233556-
dc.identifier.volume210-
dc.identifier.issue12-
dc.identifier.spage1900-
dc.identifier.epage1908-
dc.publisher.placeUnited States-

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