Identification of conserved motifs in the Westnile virus envelope essential for particle secretionReport as inadecuate




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BMC Microbiology

, 13:197

Microbe-host interactions and microbial pathogenicity

Abstract

BackgroundEnveloped viruses utilize cellular membranes to bud from infected cells. The process of virion assembly and budding is often facilitated by the presence of certain conserved motifs within viral proteins in conjunction with cellular factors. We hence examined the West Nile Virus WNV Envelope protein for the presence of any such motifs and their functional characterization.

ResultsWe identified conserved PXAP and YCYL motifs in the WNV envelope glycoprotein bearing resemblance to retroviral late domains. Disruptive mutations of PXAP to LAAL and of the highly conserved Cys in the YCYL motif, led to a severe reduction in WNV particle production. Similar motifs in case of retroviruses are known to interact with components of host sorting machinery like PXAP with Tsg101 and YXXL with Alix. However, in the case of WNV, siRNA mediated depletion of Alix or Tsg101 did not have an effect on WNV release. Molecular modeling suggested that while the PXAP motif is surface accessible and could potentially interact with cellular proteins required for WNV assembly, the YCYL motif was found to be internal with Cys important for protein folding via disulphide bonding.

ConclusionsThe conserved PXAP and YCYL motifs in the WNV envelope are indispensable for WNV particle production. Although these motifs bear sequence similarity to retroviral late domains and are essential for WNV assembly, they are functionally distinct suggesting that they are not the typical late domain like motifs of retroviruses and may play a role other than Alix-Tsg101 utilization-dependence.

KeywordsFlavivirus WNV HIV Virus assembly Late domains Alix Tsg101 AbbreviationsHIVHuman immunodeficiency virus type 1

WNVWest Nile virus

EIAVEquine infectious anemia virus

JEVJapanese encephalitis virus

YFVYellow fever virus

SLESt. Louis encephalitis virus

CCapsid

prMPre membrane

NSNon-structural

VLPsVirus like particles

ESCRTEndosomal sorting complex required for transport

Tsg101Tumor susceptibility growth factor 101

MVBMulti vesicular bodies

EREndoplasmic reticulum.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2180-13-197 contains supplementary material, which is available to authorized users.

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Author: Himanshu Garg - Raphael TC Lee - Ng Oon Tek - Sebastian Maurer-Stroh - Anjali Joshi

Source: https://link.springer.com/







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