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: | |
| 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 > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research |
| Journal Name: | eLife |
| Publisher: | eLife Sciences Publications |
| 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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