PXD037765-3

PXD037765 is an original dataset announced via ProteomeXchange.

Title	C4PR_LIV: The SARS-CoV-2 ORF3C protein interactome in Vero cells
Description	The SARS-CoV-2 genome encodes a multitude of accessory proteins. Using comparative genomic approaches, an additional accessory protein, ORF3c, has been predicted to be encoded within the ORF3a sgmRNA. Expression of ORF3c during infection has been confirmed independently by ribosome profiling. Despite ORF3c also being present in the 2002-2003 SARS-CoV, its function has remained unexplored. Here we show that ORF3c localises only to mitochondria during infection, where it inhibits innate immunity by restricting IFN-β production, but not NF-κB activation or JAK-STAT signalling downstream of type I IFN stimulation. We find that ORF3c acts after stimulation with cytoplasmic RNA helicases RIG-I or MDA5 or adaptor protein MAVS, but not after TRIF, TBK1 or phospho-IRF3 stimulation. ORF3c co-immunoprecipitates with the antiviral proteins MAVS and PGAM5 and induces MAVS cleavage by caspase-3. Unlike early lineage SARS-CoV-2 strains, delta variant strains lack intact ORF3c and do not cleave MAVS to the same extent. Together, these data provide insight into an uncharacterised mechanism of innate immune evasion by this important human pathogen. We suggest a model whereby ORF3c inhibits PGAM5-induced mitophagy and instead induces apoptosis, accompanied by caspase-3 activation. This repository contains data associated with the SARS-CoV-2 ORF3C SILAC AP-MS portions of this work.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:05:11.072.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ed Emmott
SpeciesList	scientific name: Cercopithecus aethiops (Green monkey) (Grivet); NCBI TaxID: 9534;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-10-27 02:49:48	ID requested
1	2023-10-08 06:21:15	announced
2	2023-11-14 08:13:33	announced	2023-11-14: Updated project metadata.
⏵ 3	2024-10-22 06:05:11	announced	2024-10-22: Updated project metadata.

10.1016/J.ISCI.2023.108080;

ProteomeXchange project tag: Sars-cov-2, Covid-19

submitter keyword: AP-MS,SARS-CoV-2, Virus, Coronavirus, IP, ORC3C

Ed Emmott
contact affiliation	Centre for Proteome Research, Dept. Biochemistry & Systems Biology, University of Liverpool, Liverpool, UK
contact email	e.emmott@liverpool.ac.uk
lab head
Ed Emmott
contact affiliation	Centre for Proteome Research, University of Liverpool
contact email	e.emmott@liverpool.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/2023/10/PXD037765

PRIDE project URI

• PRIDE
  1. PXD037765
     1. Label: PRIDE project
     2. Name: C4PR_LIV: The SARS-CoV-2 ORF3C protein interactome in Vero cells