Cargando…
Human cytomegalovirus interactome analysis identifies degradation hubs, domain associations and viral protein functions
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 incom...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6959991/ https://www.ncbi.nlm.nih.gov/pubmed/31873071 http://dx.doi.org/10.7554/eLife.49894 |
_version_ | 1783487694430535680 |
---|---|
author | Nobre, Luis V Nightingale, Katie Ravenhill, Benjamin J Antrobus, Robin Soday, Lior Nichols, Jenna Davies, James A Seirafian, Sepehr Wang, Eddie CY Davison, Andrew J Wilkinson, Gavin WG Stanton, Richard J Huttlin, Edward L Weekes, Michael P |
author_facet | Nobre, Luis V Nightingale, Katie Ravenhill, Benjamin J Antrobus, Robin Soday, Lior Nichols, Jenna Davies, James A Seirafian, Sepehr Wang, Eddie CY Davison, Andrew J Wilkinson, Gavin WG Stanton, Richard J Huttlin, Edward L Weekes, Michael P |
author_sort | Nobre, Luis V |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6959991 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-69599912020-01-16 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 A Seirafian, Sepehr Wang, Eddie CY Davison, Andrew J Wilkinson, Gavin WG Stanton, Richard J Huttlin, Edward L Weekes, Michael P eLife Computational and Systems Biology 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. eLife Sciences Publications, Ltd 2019-12-24 /pmc/articles/PMC6959991/ /pubmed/31873071 http://dx.doi.org/10.7554/eLife.49894 Text en © 2019, Nobre et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Computational and Systems Biology Nobre, Luis V Nightingale, Katie Ravenhill, Benjamin J Antrobus, Robin Soday, Lior Nichols, Jenna Davies, James A Seirafian, Sepehr Wang, Eddie CY Davison, Andrew J Wilkinson, Gavin WG Stanton, Richard J Huttlin, Edward L Weekes, Michael P Human cytomegalovirus interactome analysis identifies degradation hubs, domain associations and viral protein functions |
title | Human cytomegalovirus interactome analysis identifies degradation hubs, domain associations and viral protein functions |
title_full | Human cytomegalovirus interactome analysis identifies degradation hubs, domain associations and viral protein functions |
title_fullStr | Human cytomegalovirus interactome analysis identifies degradation hubs, domain associations and viral protein functions |
title_full_unstemmed | Human cytomegalovirus interactome analysis identifies degradation hubs, domain associations and viral protein functions |
title_short | Human cytomegalovirus interactome analysis identifies degradation hubs, domain associations and viral protein functions |
title_sort | human cytomegalovirus interactome analysis identifies degradation hubs, domain associations and viral protein functions |
topic | Computational and Systems Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6959991/ https://www.ncbi.nlm.nih.gov/pubmed/31873071 http://dx.doi.org/10.7554/eLife.49894 |
work_keys_str_mv | AT nobreluisv humancytomegalovirusinteractomeanalysisidentifiesdegradationhubsdomainassociationsandviralproteinfunctions AT nightingalekatie humancytomegalovirusinteractomeanalysisidentifiesdegradationhubsdomainassociationsandviralproteinfunctions AT ravenhillbenjaminj humancytomegalovirusinteractomeanalysisidentifiesdegradationhubsdomainassociationsandviralproteinfunctions AT antrobusrobin humancytomegalovirusinteractomeanalysisidentifiesdegradationhubsdomainassociationsandviralproteinfunctions AT sodaylior humancytomegalovirusinteractomeanalysisidentifiesdegradationhubsdomainassociationsandviralproteinfunctions AT nicholsjenna humancytomegalovirusinteractomeanalysisidentifiesdegradationhubsdomainassociationsandviralproteinfunctions AT daviesjamesa humancytomegalovirusinteractomeanalysisidentifiesdegradationhubsdomainassociationsandviralproteinfunctions AT seirafiansepehr humancytomegalovirusinteractomeanalysisidentifiesdegradationhubsdomainassociationsandviralproteinfunctions AT wangeddiecy humancytomegalovirusinteractomeanalysisidentifiesdegradationhubsdomainassociationsandviralproteinfunctions AT davisonandrewj humancytomegalovirusinteractomeanalysisidentifiesdegradationhubsdomainassociationsandviralproteinfunctions AT wilkinsongavinwg humancytomegalovirusinteractomeanalysisidentifiesdegradationhubsdomainassociationsandviralproteinfunctions AT stantonrichardj humancytomegalovirusinteractomeanalysisidentifiesdegradationhubsdomainassociationsandviralproteinfunctions AT huttlinedwardl humancytomegalovirusinteractomeanalysisidentifiesdegradationhubsdomainassociationsandviralproteinfunctions AT weekesmichaelp humancytomegalovirusinteractomeanalysisidentifiesdegradationhubsdomainassociationsandviralproteinfunctions |