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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, Seirafian, Sepehr, Wang, Eddie C.Y., Davison, Andrew J., Wilkinson, Gavin W.G., Stanton, Richard J., 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: Medicine
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: 29 Nov 2020 10:41
URI: http://orca-mwe.cf.ac.uk/id/eprint/128215

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