PXD031850-1

PXD031850 is an original dataset announced via ProteomeXchange.

Title	IFI16-mediated suppression of HSV-1 protein expression
Description	Human cells identify invading pathogens and activate immune signaling pathways through a wide array of pattern recognition receptors, such as DNA sensors. The interferon-inducible protein 16 (IFI16) is a nuclear DNA sensor that recognizes double-stranded DNA from a number of viral sources, including genomes of nuclear-replicating viruses such as the prevalent human pathogen, herpes simplex virus 1 (HSV-1). Upon binding to the DNA genome of HSV-1, IFI16 both induces antiviral cytokine expression and suppresses virus gene expression. Here, we use a multi-omics approach of DNA sequencing techniques paired with targeted mass spectrometry to obtain an extensive view of the interaction between IFI16 and the HSV-1 genome, and how this binding affects the viral DNA structure and protein expression. Through ChIP-seq, we find that IFI16 binds to the HSV-1 genome in a sequence-independent manner while simultaneously exhibiting broad enrichment at two loci: UL30, the viral DNA polymerase gene, and US1-US7. ATAC-seq analysis reveals that these two regions are among the most accessible stretches of DNA on the genome, thereby facilitating IFI16 binding. Accessibility of the entire HSV-1 genome is elevated upon IFI16-KO, indicating that expression of IFI16 globally induces chromatinization of viral DNA, regardless of IFI16 enrichment. Deletion of IFI16 also results in a global increase in the expression of HSV-1 proteins, as measured by parallel reaction monitoring-mass spectrometry. Altogether, we demonstrate that IFI16 interacts with the HSV-1 genome in a sequence-independent manner, and this interaction coordinates epigenetic silencing of the viral genome, resulting in decreased protein expression and virus replication.
HostingRepository	PanoramaPublic
AnnounceDate	2022-04-27
AnnouncementXML	Submission_2022-04-27_22:06:19.094.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Tim Howard
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606; scientific name: Human alphaherpesvirus 1; NCBI TaxID: 10298;
ModificationList	Carbamidomethyl
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-02-23 17:07:58	ID requested
⏵ 1	2022-04-27 22:06:19	announced

Dataset with its publication pending

submitter keyword: HSV-1, innate immunity, DNA sensing, IFI16

Ileana Cristea
contact affiliation	Princeton University
contact email	icristea@princeton.edu
lab head
Tim Howard
contact affiliation	Princeton University
contact email	th12@princeton.edu
dataset submitter

Panorama Public dataset URI