tetano
Editor, Senior Moderator
RNA. 2014 Nov 17. [Epub ahead of print]
Comparative mutational analyses of influenza A viruses.
Cheung PP1, Rogozin IB2, Choy KT1, Ng HY1, Peiris JS3, Yen HL3.
Author information
Abstract
The 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?WuhanPB2, PB1, PA, NP and RG-PR8?VN1203PB2, 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.
? 2014 Cheung et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.
KEYWORDS:
H5N1; bioinformatics; influenza A virus; mutational spectra; polymerase fidelity
PMID:
25404565
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25404565
Comparative mutational analyses of influenza A viruses.
Cheung PP1, Rogozin IB2, Choy KT1, Ng HY1, Peiris JS3, Yen HL3.
Author information
Abstract
The 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?WuhanPB2, PB1, PA, NP and RG-PR8?VN1203PB2, 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.
? 2014 Cheung et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.
KEYWORDS:
H5N1; bioinformatics; influenza A virus; mutational spectra; polymerase fidelity
PMID:
25404565
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25404565