PXD061146-1

PXD061146 is an original dataset announced via ProteomeXchange.

Title	The EZH2 inhibitor tazemetostat mitigates HIV immune evasion, reduces reservoir formation, and promotes durable CD8⁺ T-cell revitalization
Description	Persistent HIV reservoirs in CD4⁺ T-cells impede efforts to cure HIV infection. We identified overexpression of enhancer of zeste homolog 2 (EZH2) in HIV-infected CD4⁺ T-cells that survive cytotoxic T lymphocyte (CTL) exposure, suggesting a mechanism of CTL resistance. Inhibition of EZH2 with the FDA-approved drug tazemetostat increased surface expression of major histocompatibility complex class I (MHC-I) on CD4⁺ T-cells, counteracting HIV Nef–mediated MHC-I downregulation. This enhancement improved CTL-mediated elimination of HIV-infected cells and suppressed viral replication in vitro. In a participant-derived xenograft mouse model, tazemetostat elevated MHC-I and the pro-apoptotic protein BIM in CD4⁺ T-cells, facilitating CD8⁺ T-cell–mediated reduction of HIV reservoir seeding. Additionally, tazemetostat promoted sustained skewing of CD8⁺ T-cells toward less differentiated and less exhausted phenotypes. Our findings reveal EZH2 overexpression as a novel mechanism of CTL resistance and support the clinical evaluation of tazemetostat to enhance immune-mediated clearance of HIV reservoirs.
HostingRepository	PRIDE
AnnounceDate	2026-01-26
AnnouncementXML	Submission_2026-01-26_07:57:50.897.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jeffrey Johnson
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-24 12:49:57	ID requested
⏵ 1	2026-01-26 07:57:51	announced

10.1016/j.celrep.2025.115652;

Gramatica A, Miller IG, Ward AR, Khan F, Kemmer TJ, Weiler J, Huynh TT, Zumbo P, Kurland AP, Leyre L, Ren Y, Klevorn T, Copertino DC, Chukwukere U, Levinger C, Dilling TR, Linden N, Board NL, Falling Iversen E, Terry S, Mota TM, Bedir S, Clayton KL, Bosque A, MacLaren Ehui L, Kovacs C, Betel D, Johnson JR, Paiardini M, Danesh A, Jones RB, T cells toward less-exhausted phenotypes. Cell Rep, 44(5):115652(2025) [pubmed]

submitter keyword: HIV, CD8 T cells, EZH2, tazemetostat

Jeffrey Johnson
contact affiliation	Icahn School of Medicine at Mount Sinai
contact email	jeffrey.johnson@mssm.edu
lab head
Jeffrey Johnson
contact affiliation	Icahn School of Medicine at Mount Sinai
contact email	jeffrey.johnson@mssm.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/2026/01/PXD061146

PRIDE project URI

• PRIDE
  1. PXD061146
     1. Label: PRIDE project
     2. Name: The EZH2 inhibitor tazemetostat mitigates HIV immune evasion, reduces reservoir formation, and promotes durable CD8⁺ T-cell revitalization