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

Nobre, L. V. et al. (2019) Human cytomegalovirus interactome analysis identifies degradation hubs, domain associations and viral protein functions. eLife, 8, e49894. (doi:10.7554/elife.49894) (PMID:31873071) (PMCID:PMC6959991)

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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:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Nichols, Mrs Jenna and Davison, Professor Andrew
Creator Roles:
Nichols, J.Data curation, Investigation
Davison, A. J.Data curation, Writing – review and editing
Authors: Nobre, L. V., Nightingale, K., Ravenhill, B. J., Antrobus, R., Soday, L., Nichols, J., Davies, J. A., Seirafian, S., Wang, E. C.Y., Davison, A. J., Wilkinson, G. W.G., Stanton, R. J., Huttlin, E. L., and Weekes, M. P.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:eLife
Publisher:eLife Sciences Publications, Ltd
ISSN:2050-084X
ISSN (Online):2050-084X
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in eLife 8: e49894
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
656321Genomics of human cytomegalovirusAndrew DavisonMedical Research Council (MRC)MC_UU_12014/3MVLS III - CENTRE FOR VIRUS RESEARCH