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



Soh, Timothy K, Davies, Colin TR, Muenzner, Julia, Hunter, Leah M, Barrow, Henry G, Connor, Viv, Bouton, Clement R, Smith, Cameron, Emmott, Edward ORCID: 0000-0002-3239-8178, Antrobus, Robin
et al (show 3 more authors) (2020) Temporal Proteomic Analysis of Herpes Simplex Virus 1 Infection Reveals Cell-Surface Remodeling via pUL56-Mediated GOPC Degradation. CELL REPORTS, 33 (1). 108235-.

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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.

Item Type: Article
Uncontrolled Keywords: herpesvirus, virus-host interaction, immune evasion, membrane trafficking, proteasomal degradation, quantitative proteomics, uncharacterized ORF, FIG, CAL, PIST
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 22 Mar 2021 09:17
Last Modified: 18 Jan 2023 22:55
DOI: 10.1016/j.celrep.2020.108235
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3117906