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Temporal Proteomic Analysis of Herpes Simplex Virus 1 Infection Reveals Cell-Surface Remodeling via pUL56-Mediated GOPC Degradation.

Accepted version
Peer-reviewed

Type

Article

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Authors

Soh, Timothy K 
Davies, Colin TR 
Muenzner, Julia 
Hunter, Leah M 
Barrow, Henry G 

Abstract

Herpesviruses are ubiquitous in the human population and they extensively remodel the cellular environment during infection. Multiplexed quantitative proteomic analysis over the time course of herpes simplex virus 1 (HSV-1) infection was used to characterize changes in the host-cell proteome and the kinetics of viral protein production. Several host-cell proteins are targeted for rapid degradation by HSV-1, including the cellular trafficking factor Golgi-associated PDZ and coiled-coil motif-containing protein (GOPC). We show that the poorly characterized HSV-1 pUL56 directly binds GOPC, stimulating its ubiquitination and proteasomal degradation. Plasma membrane profiling reveals that pUL56 mediates specific changes to the cell-surface proteome of infected cells, including loss of interleukin-18 (IL18) receptor and Toll-like receptor 2 (TLR2), and that cell-surface expression of TLR2 is GOPC dependent. Our study provides significant resources for future investigation of HSV-host interactions and highlights an efficient mechanism whereby a single virus protein targets a cellular trafficking factor to modify the surface of infected cells.

Description

Keywords

CAL, FIG, PIST, herpesvirus, immune evasion, membrane trafficking, proteasomal degradation, quantitative proteomics, uncharacterized ORF, virus-host interaction, Adaptor Proteins, Signal Transducing, Golgi Matrix Proteins, HEK293 Cells, Herpesvirus 1, Human, Humans, Proteomics, Transfection

Journal Title

Cell Rep

Conference Name

Journal ISSN

2211-1247
2211-1247

Volume Title

33

Publisher

Elsevier BV

Rights

All rights reserved
Sponsorship
Biotechnology and Biological Sciences Research Council (BB/M021424/1)
Wellcome Trust (098406/Z/12/Z)
Wellcome Trust (098406/Z/12/B)
Wellcome Trust (108070/Z/15/Z)
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