Systematic analysis of viral genes responsible for differential virulence between American and Australian West Nile virus strains

Setoh, Yin Xiang, Prow, Natalie A., Rawle, Daniel J., Tan, Cindy Si En, Edmonds, Judith H., Hall, Roy A. and Khromykh, Alexander A. (2015) Systematic analysis of viral genes responsible for differential virulence between American and Australian West Nile virus strains. Journal of General Virology, 96 1297-1308. doi:10.1099/vir.0.000069


Author Setoh, Yin Xiang
Prow, Natalie A.
Rawle, Daniel J.
Tan, Cindy Si En
Edmonds, Judith H.
Hall, Roy A.
Khromykh, Alexander A.
Title Systematic analysis of viral genes responsible for differential virulence between American and Australian West Nile virus strains
Journal name Journal of General Virology   Check publisher's open access policy
ISSN 0022-1317
1465-2099
Publication date 2015-01
Year available 2015
Sub-type Article (original research)
DOI 10.1099/vir.0.000069
Open Access Status
Volume 96
Start page 1297
End page 1308
Total pages 12
Place of publication Reading, Berks, United Kingdom
Publisher Society for General Microbiology
Collection year 2016
Language eng
Formatted abstract
A variant Australian West Nile virus (WNV) strain, WNVNSW2011, emerged in 2011 causing an unprecedented outbreak of encephalitis in horses in south-eastern Australia. However, no human cases associated with this strain have yet been reported. Studies using mouse models for WNV pathogenesis showed that WNVNSW2011 was less virulent than the human-pathogenic American strain of WNV, New York 99 (WNVNY99). To identify viral genes and mutations responsible for the difference in virulence between WNVNSW2011 and WNVNY99 strains, we constructed chimeric viruses with substitution of large genomic regions coding for the structural genes, non-structural genes and untranslated regions, as well as seven individual non-structural gene chimeras, using a modified circular polymerase extension cloning method. Our results showed that the complete non-structural region of WNVNSW2011, when substituted with that of WNVNY99, significantly enhanced viral replication and the ability to suppress type I IFN response in cells, resulting in higher virulence in mice. Analysis of the individual non-structural gene chimeras showed a predominant contribution of WNVNY99 NS3 to increased virus replication and evasion of IFN response in cells, and to virulence in mice. Other WNVNY99 non-structural proteins (NS2A, NS4B and NS5) were shown to contribute to the modulation of IFN response. Thus a combination of non-structural proteins, likely NS2A, NS3, NS4B and NS5, is primarily responsible for the difference in virulence between WNVNSW2011 and WNVNY99 strains, and accumulative mutations within these proteins would likely be required for the Australian WNVNSW2011 strain to become significantly more virulent.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Chemistry and Molecular Biosciences
 
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Created: Fri, 29 May 2015, 14:16:46 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences