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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
KeywordsFerrets
H7N9 influenza virus
Neuraminidase inhibitors
R292K NA mutation
Resistance
Transmission
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
2021 Impact Factor: 7.759
2020 SCImago Journal Rankings: 2.690
PubMed Central ID
ISI Accession Number 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.subjectFerrets-
dc.subjectH7N9 influenza virus-
dc.subjectNeuraminidase inhibitors-
dc.subjectR292K NA mutation-
dc.subjectResistance-
dc.subjectTransmission-
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.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1093/infdis/jiu353-
dc.identifier.pmid24951824-
dc.identifier.pmcidPMC4296180-
dc.identifier.scopuseid_2-s2.0-84907919207-
dc.identifier.hkuros233556-
dc.identifier.volume210-
dc.identifier.issue12-
dc.identifier.spage1900-
dc.identifier.epage1908-
dc.identifier.isiWOS:000345771200008-
dc.publisher.placeUnited States-
dc.identifier.issnl0022-1899-

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