Identification of residues in West Nile virus premembrane protein that influence viral particle secretion and virulence

Setoh, Y. X., Prow, N. A., Hobson-Peters, J., Lobigs, M., Young, P. R., Khromykh, A. A. and Hall, R. A. (2012) Identification of residues in West Nile virus premembrane protein that influence viral particle secretion and virulence. Journal of General Virology, 93 Part 9: 1965-1975. doi:10.1099/vir.0.044453-0


Author Setoh, Y. X.
Prow, N. A.
Hobson-Peters, J.
Lobigs, M.
Young, P. R.
Khromykh, A. A.
Hall, R. A.
Title Identification of residues in West Nile virus premembrane protein that influence viral particle secretion and virulence
Journal name Journal of General Virology   Check publisher's open access policy
ISSN 0022-1317
1465-2099
Publication date 2012-09
Sub-type Article (original research)
DOI 10.1099/vir.0.044453-0
Volume 93
Issue Part 9
Start page 1965
End page 1975
Total pages 11
Place of publication Reading, Berks, United Kingdom
Publisher Society for General Microbiology
Collection year 2013
Language eng
Formatted abstract
The pre-membrane protein (prM) of West Nile virus (WNV) functions as a chaperone for correct folding of the envelope (E) protein, and prevents premature fusion during virus egress. However, little is known about its role in virulence. To investigate this, we compared the amino acid sequences of prM between a highly virulent North American strain (WNV NY99) and a weakly virulent Australian subtype (WNV KUN). Five amino acid differences occur in WNV NY99 compared with WNV KUN (I22V, H43Y, L72S, S105A and A156V). When expressed in mammalian cells, recombinant WNV NY99 prM retained native antigenic structure, and was partially exported to the cell surface. In contrast, WNV KUN prM (in the absence of the E protein) failed to express a conserved conformational epitope and was mostly retained at the pre-Golgi stage. Substitutions in residues 22 (Ile to Val) and 72 (Leu to Ser) restored the antigenic structure and cell surface expression of WNV KUN prM to the same level as that of WNV NY99, and enhanced the secretion of WNV KUN prME particles when expressed in the presence of E. Introduction of the prM substitutions into a WNV KUN infectious clone (FLSDX) enhanced the secretion of infectious particles in Vero cells, and enhanced virulence in mice. These findings highlight the role of prM in viral particle secretion and virulence, and suggest the involvement of the L72S and I22V substitutions in modulating these activities.
Keyword West Nile virus
Pre-membrane protein
prM
Virulence
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online ahead of print: 4 July 4 2012.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Chemistry and Molecular Biosciences
 
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Created: Fri, 02 Nov 2012, 10:50:51 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences