PXD050684-2

PXD050684 is an original dataset announced via ProteomeXchange.

Title	The Interferon-inducible NAMPT acts as a protein phosphoribosylase to restrict viral infection
Description	As 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.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:58:17.458.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ting-Yu Wang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	adenosine diphosphoribosyl (ADP-ribosyl) modified residue; phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2024-03-16 12:32:45	ID requested
1	2024-09-13 15:50:06	announced
⏵ 2	2024-10-22 06:58:17	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: NAMPT, HSV-1, Antivirals, phosphoribosylation

Tsui_fen Chou
contact affiliation	Proteome Exploration Laboratory, Beckman Institute, California Institute of Technology
contact email	tfchou@caltech.edu
lab head
Ting-Yu Wang
contact affiliation	Caltech
contact email	tywang@caltech.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/2024/09/PXD050684

PRIDE project URI

• PRIDE
  1. PXD050684
     1. Label: PRIDE project
     2. Name: The Interferon-inducible NAMPT acts as a protein phosphoribosylase to restrict viral infection