File Download
There are no files associated with this item.
Links for fulltext
(May Require Subscription)
- Publisher Website: 10.1038/ncomms5794
- Scopus: eid_2-s2.0-84907300612
- PMID: 25183443
- WOS: WOS:000342841400003
- Find via
Supplementary
- Citations:
- Appears in Collections:
Article: Generation and characterization of influenza A viruses with altered polymerase fidelity
Title | Generation and characterization of influenza A viruses with altered polymerase fidelity |
---|---|
Authors | |
Issue Date | 2014 |
Publisher | Nature 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? |
Abstract | Genetic 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 Identifier | http://hdl.handle.net/10722/202043 |
ISSN | 2023 Impact Factor: 14.7 2023 SCImago Journal Rankings: 4.887 |
PubMed Central ID | |
ISI Accession Number ID | |
Grants |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Cheung, PPH | - |
dc.contributor.author | Watson, SJ | - |
dc.contributor.author | Choy, KT | - |
dc.contributor.author | Sia, SF | - |
dc.contributor.author | Wong, DDY | - |
dc.contributor.author | Poon, LLM | - |
dc.contributor.author | Kellam, P | - |
dc.contributor.author | Guan, Y | - |
dc.contributor.author | Peiris, JSM | - |
dc.contributor.author | Yen, HL | - |
dc.date.accessioned | 2014-08-21T07:59:36Z | - |
dc.date.available | 2014-08-21T07:59:36Z | - |
dc.date.issued | 2014 | - |
dc.identifier.citation | Nature Communications, 2014, v. 5, article no. 4794 | - |
dc.identifier.issn | 2041-1723 | - |
dc.identifier.uri | http://hdl.handle.net/10722/202043 | - |
dc.description.abstract | Genetic 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.language | eng | - |
dc.publisher | Nature Publishing Group. The Journal's web site is located at http://www.nature.com/ncomms/index.html | - |
dc.relation.ispartof | Nature Communications | - |
dc.title | Generation and characterization of influenza A viruses with altered polymerase fidelity | - |
dc.type | Article | - |
dc.identifier.email | Cheung, PPH: pcheun5@hku.hk | - |
dc.identifier.email | Choy, KT: ktchoy@hku.hk | - |
dc.identifier.email | Sia, SF: sfsia@hkucc.hku.hk | - |
dc.identifier.email | Wong, DDY: dywong@hku.hk | - |
dc.identifier.email | Poon, LLM: llmpoon@hkucc.hku.hk | - |
dc.identifier.email | Guan, Y: yguan@hkucc.hku.hk | - |
dc.identifier.email | Peiris, JSM: malik@hkucc.hku.hk | - |
dc.identifier.email | Yen, HL: hyen@hku.hk | - |
dc.identifier.authority | Poon, LLM=rp00484 | - |
dc.identifier.authority | Guan, Y=rp00397 | - |
dc.identifier.authority | Peiris, JSM=rp00410 | - |
dc.identifier.authority | Yen, HL=rp00304 | - |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.doi | 10.1038/ncomms5794 | - |
dc.identifier.pmid | 25183443 | - |
dc.identifier.pmcid | PMC4155405 | - |
dc.identifier.scopus | eid_2-s2.0-84907300612 | - |
dc.identifier.hkuros | 233557 | - |
dc.identifier.volume | 5 | - |
dc.identifier.isi | WOS:000342841400003 | - |
dc.publisher.place | United Kingdom | - |
dc.relation.project | Control of Pandemic and Inter-pandemic Influenza | - |
dc.identifier.issnl | 2041-1723 | - |