PXD041336

PXD041336 is an original dataset announced via ProteomeXchange.

Title	An Epstein–Barr Virus Protein Interaction Map Reveals NLRP3 Inflammasome Evasion Via MAVS UFMylation
Description	Epstein-Barr virus (EBV) causes infectious mononucleosis, triggers multiple sclerosis and is associated with 200,000 cancers/year. EBV colonizes the B-cell compartment and periodically reactivates, inducing expression of 80 viral proteins. Yet much remains unknown about how EBV remodels host cells and dismantles key antiviral responses. We therefore created a proteomic map of EBV-host and EBV-EBV interactions in B-cells undergoing EBV replication, uncovering conserved herpesvirus versus EBV-specific host cell targets. The EBV-encoded G-protein coupled receptor BILF1 associated with MAVS and the UFM1 E3 ligase UFL1. Whereas UFMylation of 14-3-3 proteins drives RIG-I/MAVS signaling, BILF1-directed MAVS UFMylation instead triggered MAVS packaging into mitochondrial-derived vesicles and lysosomal proteolysis. In the absence of BILF1, EBV replication activated the NLRP3 inflammasome, which impaired viral replication and triggered pyroptosis. Our results provide a viral protein interaction network resource, reveal a UFM1-dependent pathway for selective degradation of mitochondrial cargo and highlight BILF1 as a novel therapeutic target.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:54:25.213.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Michael Weekes
SpeciesList	scientific name: Viruses; NCBI TaxID: NCBITaxon:10239; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-04-04 15:02:38	ID requested
1	2023-07-20 06:50:27	announced
2	2023-11-14 09:02:16	announced	2023-11-14: Updated project metadata.
⏵ 3	2024-10-22 05:54:26	announced	2024-10-22: Updated project metadata.

Yiu SPT, Zerbe C, Vanderwall D, Huttlin EL, Weekes MP, Gewurz BE, An Epstein-Barr virus protein interaction map reveals NLRP3 inflammasome evasion via MAVS UFMylation. Mol Cell, 83(13):2367-2386.e15(2023) [pubmed]

10.1016/j.molcel.2023.05.018;

submitter keyword: innate immunity, gasdermin D, UFMylation, herpesvirus, mitochondrial-derived vesicles, herpesvirus replication, viral G-protein coupled receptor, NLRP3 inflammasome, antiviral defense,interactome, Interleukin-1-beta

Michael Weekes
contact affiliation	Cambridge Institute for Medical Research, University of Cambridge
contact email	mpw1001@cam.ac.uk
lab head
Michael Weekes
contact affiliation	University of Cambridge
contact email	mpw1001@cam.ac.uk
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/2023/07/PXD041336

PRIDE project URI

• PRIDE
  1. PXD041336
     1. Label: PRIDE project
     2. Name: An Epstein–Barr Virus Protein Interaction Map Reveals NLRP3 Inflammasome Evasion Via MAVS UFMylation