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Article: Comparative mutational analyses of influenza A viruses

TitleComparative mutational analyses of influenza A viruses
Authors
Issue Date2015
Citation
RNA, 2015, v. 21 n. 1, p. 36-47 How to Cite?
AbstractThe error-prone RNA-dependent RNA polymerase (RdRP) and external selective pressures are the driving forces for RNA viral diversity. When confounded by selective pressures, it is difficult to assess if influenza A viruses (IAV) that have a wide host range possess comparable or distinct spontaneous mutational frequency in their RdRPs. We used in-depth bioinformatics analyses to assess the spontaneous mutational frequencies of two RdRPs derived from human seasonal (A/Wuhan/359/95; Wuhan) and H5N1 (A/Vietnam/1203/04; VN1203) viruses using the mini-genome system with a common firefly luciferase reporter serving as the template. High-fidelity reverse transcriptase was applied to generate high-quality mutational spectra which allowed us to assess and compare the mutational frequencies and mutable motifs along a target sequence of the two RdRPs of two different subtypes. We observed correlated mutational spectra (τ correlation P < 0.0001), comparable mutational frequencies (H3N2:5.8 ± 0.9; H5N1:6.0 ± 0.5), and discovered a highly mutable motif "(A)AAG" for both Wuhan and VN1203 RdRPs. Results were then confirmed with two recombinant A/Puerto Rico/8/34 (PR8) viruses that possess RdRP derived from Wuhan or VN1203 (RG-PR8×Wuhan(PB2, PB1, PA, NP) and RG-PR8×VN1203(PB2, PB1, PA, NP)). Applying novel bioinformatics analysis on influenza mutational spectra, we provide a platform for a comprehensive analysis of the spontaneous mutation spectra for an RNA virus.
Persistent Identifierhttp://hdl.handle.net/10722/207841
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorCheung, PPHen_US
dc.contributor.authorRogozin, IBen_US
dc.contributor.authorChoy, KTen_US
dc.contributor.authorNg, IHYen_US
dc.contributor.authorPeiris, JSMen_US
dc.contributor.authorYen, Hen_US
dc.date.accessioned2015-01-19T11:23:04Z-
dc.date.available2015-01-19T11:23:04Z-
dc.date.issued2015en_US
dc.identifier.citationRNA, 2015, v. 21 n. 1, p. 36-47en_US
dc.identifier.urihttp://hdl.handle.net/10722/207841-
dc.description.abstractThe error-prone RNA-dependent RNA polymerase (RdRP) and external selective pressures are the driving forces for RNA viral diversity. When confounded by selective pressures, it is difficult to assess if influenza A viruses (IAV) that have a wide host range possess comparable or distinct spontaneous mutational frequency in their RdRPs. We used in-depth bioinformatics analyses to assess the spontaneous mutational frequencies of two RdRPs derived from human seasonal (A/Wuhan/359/95; Wuhan) and H5N1 (A/Vietnam/1203/04; VN1203) viruses using the mini-genome system with a common firefly luciferase reporter serving as the template. High-fidelity reverse transcriptase was applied to generate high-quality mutational spectra which allowed us to assess and compare the mutational frequencies and mutable motifs along a target sequence of the two RdRPs of two different subtypes. We observed correlated mutational spectra (τ correlation P < 0.0001), comparable mutational frequencies (H3N2:5.8 ± 0.9; H5N1:6.0 ± 0.5), and discovered a highly mutable motif "(A)AAG" for both Wuhan and VN1203 RdRPs. Results were then confirmed with two recombinant A/Puerto Rico/8/34 (PR8) viruses that possess RdRP derived from Wuhan or VN1203 (RG-PR8×Wuhan(PB2, PB1, PA, NP) and RG-PR8×VN1203(PB2, PB1, PA, NP)). Applying novel bioinformatics analysis on influenza mutational spectra, we provide a platform for a comprehensive analysis of the spontaneous mutation spectra for an RNA virus.en_US
dc.languageengen_US
dc.relation.ispartofRNAen_US
dc.titleComparative mutational analyses of influenza A virusesen_US
dc.typeArticleen_US
dc.identifier.emailCheung, PPH: pcheun5@hku.hken_US
dc.identifier.emailChoy, KT: ktchoy@hku.hken_US
dc.identifier.emailNg, IHY: ihyng@hkucc.hku.hken_US
dc.identifier.emailPeiris, JSM: malik@hkucc.hku.hken_US
dc.identifier.emailYen, H: hyen@hku.hken_US
dc.identifier.authorityPeiris, JSM=rp00410en_US
dc.identifier.authorityYen, H=rp00304en_US
dc.identifier.doi10.1261/rna.045369.114en_US
dc.identifier.pmcidPMC4274636-
dc.identifier.hkuros242088en_US
dc.identifier.volume21en_US
dc.identifier.issue1en_US
dc.identifier.spage36en_US
dc.identifier.epage47en_US

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