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Article: Comparable fitness and transmissibility between oseltamivir-resistant pandemic 2009 and seasonal H1N1 influenza viruses with the H275Y neuraminidase mutation

TitleComparable fitness and transmissibility between oseltamivir-resistant pandemic 2009 and seasonal H1N1 influenza viruses with the H275Y neuraminidase mutation
Authors
Issue Date2012
PublisherAmerican Society for Microbiology. The Journal's web site is located at http://jvi.asm.org/
Citation
Journal of Virology, 2012, v. 86 n. 19, p. 10558-10570 How to Cite?
AbstractLimited antiviral compounds are available for the control of influenza, and the emergence of resistant variants would further narrow the options for defense. The H275Y neuraminidase (NA) mutation, which confers resistance to oseltamivir carboxylate, has been identified among the seasonal H1N1 and 2009 pandemic influenza viruses; however, those H275Y resistant variants demonstrated distinct epidemiological outcomes in humans. Specifically, dominance of the H275Y variant over the oseltamivir-sensitive viruses was only reported for a seasonal H1N1 variant during 2008-2009. Here, we systematically analyze the effect of the H275Y NA mutation on viral fitness and transmissibility of A(H1N1)pdm09 and seasonal H1N1 influenza viruses. The NA genes from A(H1N1)pdm09 A/California/04/09 (CA04), seasonal H1N1 A/New Caledonia/20/1999 (NewCal), and A/Brisbane/59/2007 (Brisbane) were individually introduced into the genetic background of CA04. The H275Y mutation led to reduced NA enzyme activity, an increased K(m) for 3'-sialylactose or 6'-sialylactose, and decreased infectivity in mucin-secreting human airway epithelial cells compared to the oseltamivir-sensitive wild-type counterparts. Attenuated pathogenicity in both RG-CA04(NA-H275Y) and RG-CA04 x Brisbane(NA-H275Y) viruses was observed in ferrets compared to RG-CA04 virus, although the transmissibility was minimally affected. In parallel experiments using recombinant Brisbane viruses differing by hemagglutinin and NA, comparable direct contact and respiratory droplet transmissibilities were observed among RG-NewCal(HA,NA), RG-NewCal(HA,NA-H275Y), RG-Brisbane(HA,NA-H275Y), and RG-NewCal(HA) x Brisbane(NA-H275Y) viruses. Our results demonstrate that, despite the H275Y mutation leading to a minor reduction in viral fitness, the transmission potentials of three different antigenic strains carrying this mutation were comparable in the naive ferret model.
Persistent Identifierhttp://hdl.handle.net/10722/161160
ISSN
2015 Impact Factor: 4.606
2015 SCImago Journal Rankings: 3.347
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWong, DDYen_US
dc.contributor.authorChoy, KTen_US
dc.contributor.authorChan, RWYen_US
dc.contributor.authorSia, SFen_US
dc.contributor.authorChiu, HPen_US
dc.contributor.authorCheung, PHPen_US
dc.contributor.authorChan, MCWen_US
dc.contributor.authorPeiris, JSMen_US
dc.contributor.authorYen, HLen_US
dc.date.accessioned2012-08-16T06:39:39Z-
dc.date.available2012-08-16T06:39:39Z-
dc.date.issued2012en_US
dc.identifier.citationJournal of Virology, 2012, v. 86 n. 19, p. 10558-10570en_US
dc.identifier.issn0022-538X-
dc.identifier.urihttp://hdl.handle.net/10722/161160-
dc.description.abstractLimited antiviral compounds are available for the control of influenza, and the emergence of resistant variants would further narrow the options for defense. The H275Y neuraminidase (NA) mutation, which confers resistance to oseltamivir carboxylate, has been identified among the seasonal H1N1 and 2009 pandemic influenza viruses; however, those H275Y resistant variants demonstrated distinct epidemiological outcomes in humans. Specifically, dominance of the H275Y variant over the oseltamivir-sensitive viruses was only reported for a seasonal H1N1 variant during 2008-2009. Here, we systematically analyze the effect of the H275Y NA mutation on viral fitness and transmissibility of A(H1N1)pdm09 and seasonal H1N1 influenza viruses. The NA genes from A(H1N1)pdm09 A/California/04/09 (CA04), seasonal H1N1 A/New Caledonia/20/1999 (NewCal), and A/Brisbane/59/2007 (Brisbane) were individually introduced into the genetic background of CA04. The H275Y mutation led to reduced NA enzyme activity, an increased K(m) for 3'-sialylactose or 6'-sialylactose, and decreased infectivity in mucin-secreting human airway epithelial cells compared to the oseltamivir-sensitive wild-type counterparts. Attenuated pathogenicity in both RG-CA04(NA-H275Y) and RG-CA04 x Brisbane(NA-H275Y) viruses was observed in ferrets compared to RG-CA04 virus, although the transmissibility was minimally affected. In parallel experiments using recombinant Brisbane viruses differing by hemagglutinin and NA, comparable direct contact and respiratory droplet transmissibilities were observed among RG-NewCal(HA,NA), RG-NewCal(HA,NA-H275Y), RG-Brisbane(HA,NA-H275Y), and RG-NewCal(HA) x Brisbane(NA-H275Y) viruses. Our results demonstrate that, despite the H275Y mutation leading to a minor reduction in viral fitness, the transmission potentials of three different antigenic strains carrying this mutation were comparable in the naive ferret model.-
dc.languageengen_US
dc.publisherAmerican Society for Microbiology. The Journal's web site is located at http://jvi.asm.org/-
dc.relation.ispartofJournal of Virologyen_US
dc.rightsJournal of Virology. Copyright © American Society for Microbiology.-
dc.rightsCopyright © American Society for Microbiology, [Journal of Virology, 2012, v. 86 n. 19, p. 10558-10570]-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleComparable fitness and transmissibility between oseltamivir-resistant pandemic 2009 and seasonal H1N1 influenza viruses with the H275Y neuraminidase mutationen_US
dc.typeArticleen_US
dc.identifier.emailChoy, KT: ktchoy@hku.hken_US
dc.identifier.emailChan, RWY: reneewy@hku.hken_US
dc.identifier.emailSia, SF: sfsia@hkucc.hku.hken_US
dc.identifier.emailChiu, HP: hpchiu@hku.hken_US
dc.identifier.emailChan, MCW: mchan@hku.hken_US
dc.identifier.emailPeiris, JSM: malik@hkucc.hku.hken_US
dc.identifier.emailYen, HL: hyen@hku.hken_US
dc.identifier.authorityChan, WY=rp01596en_US
dc.identifier.authorityChan, MCW=rp00420en_US
dc.identifier.authorityPeiris, JSM=rp00410en_US
dc.identifier.authorityYen, H=rp00304en_US
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1128/JVI.00985-12-
dc.identifier.pmid22811535-
dc.identifier.pmcidPMC3457312-
dc.identifier.scopuseid_2-s2.0-84869067378-
dc.identifier.hkuros204679en_US
dc.identifier.hkuros226283-
dc.identifier.volume86-
dc.identifier.issue19-
dc.identifier.spage10558-
dc.identifier.epage10570-
dc.identifier.eissn1098-5514-
dc.identifier.isiWOS:000308740700031-
dc.publisher.placeUnited States-

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