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Whole-cell and plasma membrane proteomics of herpes simplex virus-1 infection reveals cell surface remodelling via pUL56-mediated GOPC degradation

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 (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 GOPC. We show that the poorly-characterized HSV-1 pUL56 directly binds GOPC, stimulating its ubiquitination and proteasomal degradation. Plasma membrane profiling revealed that pUL56 mediates specific changes to the cell surface proteome of infected cells, including loss of IL18 receptor and Toll-like receptor 2, and that cell surface expression of Toll-like receptor 2 is GOPC-dependent. Our study provides significant resources for future investigation of HSV-host interactions and highlights an unanticipated and efficient mechanism whereby a single virus protein targets a cellular trafficking factor to modify the surface of infected cells.

INSTRUMENT(S): Orbitrap Fusion Lumos, Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human) Human Alphaherpesvirus 1

TISSUE(S): Cell Culture, Keratinocyte

SUBMITTER: Leah Hunter

LAB HEAD: Michael Weekes

PROVIDER: PXD021351 | Pride | 2020-10-15

REPOSITORIES: Pride

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			Action	DRS
	Detailsofsamplesandrawfiles.docx	Other
	PMP_GOPC_KO_F1.raw	Raw
	PMP_GOPC_KO_F2.raw	Raw
	PMP_GOPC_KO_F3.raw	Raw
	PMP_GOPC_KO_F4.raw	Raw

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