Cell Reports (Oct 2020)

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

  • Timothy K. Soh,
  • Colin T.R. Davies,
  • Julia Muenzner,
  • Leah M. Hunter,
  • Henry G. Barrow,
  • Viv Connor,
  • Clément R. Bouton,
  • Cameron Smith,
  • Edward Emmott,
  • Robin Antrobus,
  • Stephen C. Graham,
  • Michael P. Weekes,
  • Colin M. Crump

Journal volume & issue
Vol. 33, no. 1
p. 108235

Abstract

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Summary: 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.

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