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Mechanistic Understanding of N-Glycosylation in Ebola Virus Glycoprotein Maturation and Function.

Mechanistic Understanding of N-Glycosylation in Ebola Virus Glycoprotein Maturation and Function.
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Wang B, Wang Y, Frabutt DA, Zhang X, Yao X, Hu D, Zhang Z, Liu C, Zheng S, Xiang SH, Zheng YH,


Wang B, Wang Y, Frabutt DA, Zhang X, Yao X, Hu D, Zhang Z, Liu C, Zheng S, Xiang SH, Zheng YH, (click to view)

Wang B, Wang Y, Frabutt DA, Zhang X, Yao X, Hu D, Zhang Z, Liu C, Zheng S, Xiang SH, Zheng YH,

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The Journal of biological chemistry 2017 02 14() pii 10.1074/jbc.M116.768168

Abstract

The Ebola virus (EBOV) trimeric envelope glycoprotein (GP) precursors are cleaved into the receptor-binding GP1 and the fusion-mediating GP2 subunits and incorporated into virions to initiate infection. GP1 and GP2 form heterodimers, which have 15 or 2 N-glycosylation sites (NGSs), respectively. Here, we investigated the mechanism of how N-glycosylation contributes to GP expression, maturation, and function. As reported before, we found that although GP1 NGSs are not critical, the two GP2 NGSs, N563 and N618, are essential to the GP function. Further analysis uncovered that N563 and N618 regulate GP processing, demannosylation, oligomerization, and conformation. Consequently, these two NGSs are required for GP incorporation into EBOV-like particles (E-VLP) and HIV-1 pseudovirions, and determine viral transduction efficiency. Using CRISPR/Cas9 technology, we knocked out the two classical endoplasmic reticulum (ER) chaperones calnexin (CNX) and/or calreticulin (CRT) and found that both CNX and CRT increase the GP expression. Nevertheless, NGSs are not required for the GP interaction with CNX or CRT. Together, we conclude that although N563 and N618 are not required for EBOV GP expression, they synergistically regulate its maturation, which determines its functionality.

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