Human cytomegalovirus interactome analysis identifies degradation hubs, domain associations and viral protein functions.

Autor:	Nobre LV; Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom., Nightingale K; Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom., Ravenhill BJ; Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom., Antrobus R; Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom., Soday L; Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom., Nichols J; MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom., Davies JA; Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom., Seirafian S; Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom., Wang EC; Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom., Davison AJ; MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom., Wilkinson GW; Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom., Stanton RJ; Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom., Huttlin EL; Department of Cell Biology, Harvard Medical School, Boston, United States., Weekes MP; Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2019 Dec 24; Vol. 8. Date of Electronic Publication: 2019 Dec 24.
DOI:	10.7554/eLife.49894
Abstrakt:	Human cytomegalovirus (HCMV) extensively modulates host cells, downregulating >900 human proteins during viral replication and degrading ≥133 proteins shortly after infection. The mechanism of degradation of most host proteins remains unresolved, and the functions of many viral proteins are incompletely characterised. We performed a mass spectrometry-based interactome analysis of 169 tagged, stably-expressed canonical strain Merlin HCMV proteins, and two non-canonical HCMV proteins, in infected cells. This identified a network of >3400 virus-host and >150 virus-virus protein interactions, providing insights into functions for multiple viral genes. Domain analysis predicted binding of the viral UL25 protein to SH3 domains of NCK Adaptor Protein-1. Viral interacting proteins were identified for 31/133 degraded host targets. Finally, the uncharacterised, non-canonical ORFL147C protein was found to interact with elements of the mRNA splicing machinery, and a mutational study suggested its importance in viral replication. The interactome data will be important for future studies of herpesvirus infection. Competing Interests: LN, KN, BR, RA, LS, JN, JD, SS, EW, AD, GW, RS, EH, MW No competing interests declared (© 2019, Nobre et al.)
Databáze:	MEDLINE
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