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

Nobre, Luis V., Nightingale, Katie, Ravenhill, Benjamin J., Antrobus, Robin, Soday, Lior, Nichols, Jenna, Davies, James ORCID: https://orcid.org/0000-0003-3569-4500, Seirafian, Sepehr, Wang, Eddie C.Y. ORCID: https://orcid.org/0000-0002-2243-4964, Davison, Andrew J., Wilkinson, Gavin W.G., Stanton, Richard J. ORCID: https://orcid.org/0000-0002-6799-1182, Huttlin, Edward L. and Weekes, Michael P. 2019. Human cytomegalovirus interactome analysis identifies degradation hubs, domain associations and viral protein functions. eLife 8 , e49894. 10.7554/eLife.49894

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Abstract

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 >3,400 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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine Research Institutes & Centres > Systems Immunity Research Institute (SIURI)
Publisher:	eLife Sciences Publications
ISSN:	2050-084X
Funders:	Medical Research Council, Wellcome Trust
Date of First Compliant Deposit:	7 January 2020
Date of Acceptance:	24 December 2019
Last Modified:	22 Nov 2024 21:00
URI:	https://orca.cardiff.ac.uk/id/eprint/128215

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