PXD018773

PXD018773 is an original dataset announced via ProteomeXchange.

Title	Identification of SLFN5 as an intrinsic inhibitor of viral transcription antagonized by the herpes simplex virus ubiquitin ligase ICP0
Description	Intrinsic antiviral host factors are proteins that can confer cellular defense by limiting virus replication. Viruses hijack ubiquitin machinery to modify the cellular proteome to subvert these host defenses. The herpes simplex virus 1 (HSV-1) expresses ICP0, which functions as an E3 ubiquitin ligase required to promote infection. Cellular substrates of ICP0 have been discovered as host barriers to infection but the mechanisms for inhibition of viral gene expression are not fully understood. To identify new restriction factors antagonized by ICP0, we compared the proteomes associated with viral DNA (vDNA) during HSV-1 infection with wild-type (WT) virus and a mutant lacking functional ICP0 (ΔICP0). We identified the cellular protein Schlafen 5 (SLFN5) as a new ICP0 target that binds vDNA during HSV-1 ΔICP0 infection. We demonstrated that ICP0 mediates ubiquitination of SLFN5 which leads to its proteasomal degradation. In the absence of ICP0, we demonstrate SLFN5 binds vDNA to represses HSV-1 transcription by limiting accessibility of RNA polymerase II to viral promoters. These results identify SLFN5 as a new restriction factor that inhibits viral transcription and document the first viral countermeasure reported to overcome SLFN antiviral activity.
HostingRepository	PRIDE
AnnounceDate	2020-09-14
AnnouncementXML	Submission_2020-09-13_22:45:42.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Katarzyna Kulej
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606; scientific name: Human alphaherpesvirus 1 strain 17; NCBI TaxID: 10299;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2020-04-24 01:18:08	ID requested
⏵ 1	2020-09-13 22:45:42	announced

Dataset with its publication pending

submitter keyword: Herpes Simplex Virus, HSV-1, ICP0, dICP0, iPOND, SLFN5, ubiquitin

Benjamin A. Garcia
contact affiliation	Department of Biochemistry and Biophysics Smilow Center for Translational Research Perelman School of Medicine University of Pennsylvania Room 9-124 (office) 3400 Civic Center Blvd Philadelphia, PA 19104 215-573-9423 (office)
contact email	bgarci@pennmedicine.upenn.edu
lab head
Katarzyna Kulej
contact affiliation	Children's Hospital of Philadelphia
contact email	kulej.katarzyna@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD018773
     1. Label: PRIDE project
     2. Name: Identification of SLFN5 as an intrinsic inhibitor of viral transcription antagonized by the herpes simplex virus ubiquitin ligase ICP0