PXD005276

PXD005276 is an original dataset announced via ProteomeXchange.

Title	Kinome profiling upon HCMV infection using the MIB-MS approach
Description	Human cytomegalovirus (HCMV) is a significant cause of disease in immune-compromised adults and immune naïve newborns. No vaccine exists to prevent HCMV infection, and current antiviral therapies have toxic side effects that limit the duration and intensity of their use. There is thus an urgent need for new strategies to treat HCMV and repurposing existing drugs as antivirals is an attractive approach. Virus-induced changes in infected cells are often driven by changes in cellular kinase activity, leading us to hypothesize that defining the complement of kinases (the kinome), whose activity or expression is altered during infection would identify existing kinase inhibitors that could be repurposed as new antivirals. To this end, we applied a recently developed technique, MIB-MS kinome profiling, to quantitatively measure perturbations in >240 cellular kinases simultaneously in cells infected with a laboratory-adapted (AD169) or clinical (TB40E) HCMV strain using a label-free approach. Significant time-dependent changes for multiple kinases including cell cycle, receptor tyrosine and mitotic kinases were observed. Based on these data, we tested antiviral activity of 14 kinase inhibitors, and the most potent inhibitor blocked HCMV early gene expression and viral DNA accumulation. These results show the utility of kinome profiling to screen kinase inhibitors that can be repurposed as antivirals.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:33:51.510.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Laura Herring
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2016-11-04 10:03:44	ID requested
1	2017-03-20 07:17:12	announced
⏵ 2	2024-10-22 04:33:53	announced	2024-10-22: Updated project metadata.

Arend KC, Lenarcic EM, Vincent HA, Rashid N, Lazear E, McDonald IM, Gilbert TS, East MP, Herring LE, Johnson GL, Graves LM, Moorman NJ, Kinome Profiling Identifies Druggable Targets for Novel Human Cytomegalovirus (HCMV) Antivirals. Mol Cell Proteomics, 16(4 suppl 1):S263-S276(2017) [pubmed]

10.1074/mcp.M116.065375;

submitter keyword: HCMV, human herpesvirus, kinase inhibitors,kinome, antivirals, virology, label-free quantitation

Nathaniel J. Moorman
contact affiliation	Department of Microbiology & Immunology UNC School of Medicine UNC-Chapel Hill
contact email	nathaniel_moorman@med.unc.edu
lab head
Laura Herring
contact affiliation	UNC-Chapel Hill
contact email	laura_herring@med.unc.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/03/PXD005276

PRIDE project URI

• PRIDE
  1. PXD005276
     1. Label: PRIDE project
     2. Name: Kinome profiling upon HCMV infection using the MIB-MS approach