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Article: Generation and characterization of influenza A viruses with altered polymerase fidelity

TitleGeneration and characterization of influenza A viruses with altered polymerase fidelity
Authors
Issue Date2014
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/ncomms/index.html
Citation
Nature Communications, 2014, v. 5, article no. 4794 How to Cite?
AbstractGenetic diversity of influenza A viruses (IAV) acquired through the error-prone RNA-dependent RNA polymerase (RdRP) or through genetic reassortment enables perpetuation of IAV in humans through epidemics or pandemics. Here, to assess the biological significance of genetic diversity acquired through RdRP, we characterize an IAV fidelity variant derived from passaging a seasonal H3N2 virus in the presence of ​ribavirin, a purine analogue that increases ​guanosine-to-​adenosine mutations. We demonstrate that a single ​PB1-V43I mutation increases selectivity to ​guanosine in A/Wuhan/359/95 (H3N2) and A/Vietnam/1203/04 (H5N1) viruses. The H5N1 ​PB1-V43I-recombinant virus replicates to comparable titres as the wild-type virus in vitro or in the mouse lungs. However, a decrease in viral population diversity at day 3 post inoculation is associated with a tenfold reduced lethality and neurotropism in mice. Applying a fidelity variant with reduced mutational frequency, we provide direct experimental evidence for the role of genetic diversity in IAV pathogenesis.
Persistent Identifierhttp://hdl.handle.net/10722/202043
ISSN
2015 Impact Factor: 11.329
2015 SCImago Journal Rankings: 6.539
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorCheung, PPH-
dc.contributor.authorWatson, SJ-
dc.contributor.authorChoy, KT-
dc.contributor.authorSia, SF-
dc.contributor.authorWong, DDY-
dc.contributor.authorPoon, LLM-
dc.contributor.authorKellam, P-
dc.contributor.authorGuan, Y-
dc.contributor.authorPeiris, JSM-
dc.contributor.authorYen, HL-
dc.date.accessioned2014-08-21T07:59:36Z-
dc.date.available2014-08-21T07:59:36Z-
dc.date.issued2014-
dc.identifier.citationNature Communications, 2014, v. 5, article no. 4794-
dc.identifier.issn2041-1723-
dc.identifier.urihttp://hdl.handle.net/10722/202043-
dc.description.abstractGenetic diversity of influenza A viruses (IAV) acquired through the error-prone RNA-dependent RNA polymerase (RdRP) or through genetic reassortment enables perpetuation of IAV in humans through epidemics or pandemics. Here, to assess the biological significance of genetic diversity acquired through RdRP, we characterize an IAV fidelity variant derived from passaging a seasonal H3N2 virus in the presence of ​ribavirin, a purine analogue that increases ​guanosine-to-​adenosine mutations. We demonstrate that a single ​PB1-V43I mutation increases selectivity to ​guanosine in A/Wuhan/359/95 (H3N2) and A/Vietnam/1203/04 (H5N1) viruses. The H5N1 ​PB1-V43I-recombinant virus replicates to comparable titres as the wild-type virus in vitro or in the mouse lungs. However, a decrease in viral population diversity at day 3 post inoculation is associated with a tenfold reduced lethality and neurotropism in mice. Applying a fidelity variant with reduced mutational frequency, we provide direct experimental evidence for the role of genetic diversity in IAV pathogenesis.-
dc.languageeng-
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/ncomms/index.html-
dc.relation.ispartofNature Communications-
dc.titleGeneration and characterization of influenza A viruses with altered polymerase fidelity-
dc.typeArticle-
dc.identifier.emailCheung, PPH: pcheun5@hku.hk-
dc.identifier.emailChoy, KT: ktchoy@hku.hk-
dc.identifier.emailSia, SF: sfsia@hkucc.hku.hk-
dc.identifier.emailWong, DDY: dywong@hku.hk-
dc.identifier.emailPoon, LLM: llmpoon@hkucc.hku.hk-
dc.identifier.emailGuan, Y: yguan@hkucc.hku.hk-
dc.identifier.emailPeiris, JSM: malik@hkucc.hku.hk-
dc.identifier.emailYen, HL: hyen@hku.hk-
dc.identifier.authorityPoon, LLM=rp00484-
dc.identifier.authorityGuan, Y=rp00397-
dc.identifier.authorityPeiris, JSM=rp00410-
dc.identifier.authorityYen, HL=rp00304-
dc.identifier.doi10.1038/ncomms5794-
dc.identifier.pmid25183443-
dc.identifier.pmcidPMC4155405-
dc.identifier.hkuros233557-
dc.identifier.volume5-
dc.publisher.placeUnited Kingdom-

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