Identification of residues in West Nile virus premembrane protein that influence viral particle secretion and virulence
Date
2012
Authors
Setoh, Y.X.
Prow, N.A.
Hobson Peters, J.
Lobigs, M.
Young, P.R.
Khromykh, A.A.
Hall, R.A.
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Journal article
Citation
Journal of General Virology, 2012; 93(PART 9):1965-1975
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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.
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Copyright 2012 SGM. This article is open access and allows authors and their funding bodies to make published articles freely available online from the time of publication, upon payment of an Article Processing Charge (APC) (https://jgv.microbiologyresearch.org/about/open-access-policy)