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PXD050684

PXD050684 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleThe Interferon-inducible NAMPT acts as a protein phosphoribosylase to restrict viral infection
DescriptionAs obligate intracellular pathogens, viruses often activate host metabolic enzymes to supply intermediates that support progeny production. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of the salvage NAD+ synthesis, is an interferon-inducible protein that inhibits the replication of several RNA and DNA viruses with unknown mechanism. Here we report that NAMPT restricts herpes simplex virus 1 (HSV-1) replication via phosphoribosyl-hydrolase activity toward key viral structural proteins, independent of NAD+ synthesis. Deep mining of enriched phosphopeptides of HSV-1-infected cells identified phosphoribosylated viral structural proteins, particularly glycoproteins and tegument proteins. Indeed, NAMPT dephosphoribosylates viral proteins in vitro and in cells. Chimeric and recombinant HSV-1 carrying phosphoribosylation-resistant mutations show that phosphoribosylation promotes the incorporation of structural proteins into HSV-1 virions and subsequent virus entry. Moreover, loss of NAMPT renders mice highly susceptible to HSV-1 infection. The work describes a hidden enzyme activity of a metabolic enzyme in viral infection and host defense, offering a system to interrogate roles of phosphoribosylation in metazoans.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_06:58:17.458.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterTing-Yu Wang
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListadenosine diphosphoribosyl (ADP-ribosyl) modified residue; phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Eclipse
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-03-16 12:32:45ID requested
12024-09-13 15:50:06announced
22024-10-22 06:58:17announced2024-10-22: Updated project metadata.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: NAMPT, HSV-1, Antivirals, phosphoribosylation
Contact List
Tsui_fen Chou
contact affiliationProteome Exploration Laboratory, Beckman Institute, California Institute of Technology
contact emailtfchou@caltech.edu
lab head
Ting-Yu Wang
contact affiliationCaltech
contact emailtywang@caltech.edu
dataset submitter
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Dataset FTP location
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PRIDE project URI
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