PXD034648

PXD034648 is an original dataset announced via ProteomeXchange.

Title	SARS-CoV-2 spike sequence dictates host TP53 activity and COVID-19 pathogenicity
Description	SARS-CoV-2 induces widespread transcriptomic changes in host cells upon infection, in part through activation and modulation of innate immunity pathways and downstream gene regulation. However, the mechanisms by which SARS-CoV-2 and its evolutionary variants differentially affect host cell transcriptomic states remain largely unclear. Through chromatin proteomic (iDAPT-MS) analysis, we found that although SARS-CoV-2 and other pathogenic coronaviruses exhibit similar proteomic shifts on chromatin, SARS-CoV-2 uniquely promotes TP53 nuclear accumulation and activation. Parallel assessment of SARS-CoV-2 viral protein expression on host chromatin states (ATAC-seq) identifies intracellular spike protein as a key determinant of virus-mediated chromatin accessibility changes. Multilevel chromatin profiling reveals increased TP53 nuclear accumulation, TP53-associated chromatin accessibility changes, and TP53 target gene activation upon expression of SARS-CoV-2 alpha (B.1.1.7) and delta (B.1.617.2) spike variants relative to the ancestral spike sequence. TP53, ACE2, and furin cleavage are required for these changes, driving decreased cellular proliferation, increased cellular senescence, and increased cytokine release. Finally, BA.1 but not BA.2, BA.2.12.1, nor BA.4/BA.5 spike expression leads to attenuated TP53 activity and fusogenicity relative to ancestral spike. Our findings implicate spike-mediated host TP53 activation as a “rheostat” of COVID-19 pathogenicity.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:02:57.287.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Joao Paulo
SpeciesList	scientific name: Chlorocebus sabaeus; NCBI TaxID: 60711;
ModificationList	monohydroxylated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2022-06-19 05:09:50	ID requested
1	2023-09-09 13:38:30	announced
⏵ 2	2024-10-22 06:02:57	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

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

submitter keyword: iDAPT-MS, SARS-CoV-2, COVID-19,TP53, spike

Frank J. Slack
contact affiliation	Department of Pathology Beth Israel Deaconess Medical Center Harvard Medical School, Boston, MA, 02115, USA.
contact email	fslack@bidmc.harvard.edu
lab head
Joao Paulo
contact affiliation	Harvard Medical School
contact email	joao_paulo@post.harvard.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/2023/09/PXD034648

PRIDE project URI

• PRIDE
  1. PXD034648
     1. Label: PRIDE project
     2. Name: SARS-CoV-2 spike sequence dictates host TP53 activity and COVID-19 pathogenicity