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

Published version
Peer-reviewed

Type

Article

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Authors

Ravenhill, Benjamin J 
Antrobus, Robin 

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 >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.

Description

Keywords

Human, Virus, Microbiology, Infectious disease, Protein-protein interaction, Proteomics, Human cytomegalovirus, systems biology, computational biology, Immune Evasion, Host-pathogen Interaction, Systems Virology

Journal Title

Conference Name

Journal ISSN

2050-084X

Volume Title

Publisher

Sponsorship
NIH HHS (U24 HG006673)
Medical Research Council (MR/P001602/1, MC_UU_12014/3, MR/L018373/1, MR/S00971X/1)
Wellcome Trust (WT090323MA, 108070/Z/15/Z)