PXD042550-1

PXD042550 is an original dataset announced via ProteomeXchange.

Title	Persistent Type I Interferon Signaling in the Brain of People with HIV under ART with Cognitive Impairment
Description	To examine the mechanisms that drive persistent neuroinflammation, we analyzed the proteome from 27 HIV-infected brains on antiretroviral therapy (ART) with different stages of HIV-associated neurocognitive disorders (HAND) by tandem mass tag quantitative proteomics. We observed that 73.3% of the upregulated proteins were from immune pathways, among which 36.4% were within the type I interferon (IFN-I) signaling. Single-cell RNA-seq analysis revealed that IFN-I signaling persisted in the brain microglia isolated from people with HIV (PWH) on suppressive ART. During the acute HIV infection, IFN-I signaling was activated in astrocytes in the brain organoids while it remained activated in the HAND brains even with undetectable HIV. HAND progression was associated with human endogenous retroviruses-W (HERV-W) Env expression in the HAND brains on suppressive ART. When overexpressed, HERV-W Env induced IFNβ in astrocytes. These findings point to a persistent IFN-I activation in the glial cells in HAND brains, suggesting a mechanistic link of sustained neuroinflammation with the prevalence of cognitive impairment in HAND receiving effective ART.
HostingRepository	PRIDE
AnnounceDate	2025-08-25
AnnouncementXML	Submission_2025-08-24_19:22:09.801.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ling Xie
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-05-30 12:57:06	ID requested
⏵ 1	2025-08-24 19:22:10	announced

Tang Y, Xie L, Shabangu CS, Li D, da Silva Prates G, Manickam A, Wong LM, Chaillon A, Browne EP, Gianella S, Ho W, Margolis DM, Chen X, Hu W, Jiang G, Persistent type I interferon signaling within the brain of people with HIV on ART with cognitive impairment. PLoS Pathog, 21(8):e1013411(2025) [pubmed]

10.1371/journal.ppat.1013411;

submitter keyword: IFN, HIV-associated neurocognitive disorders (HAND), proteome

Guochun Jiang
contact affiliation	UNC HIV Cure Center & Department of Biochemistry and Biophysics University of North Carolina
contact email	guochun_jiang@med.unc.edu
lab head
Ling Xie
contact affiliation	UNC at Chapel Hill
contact email	xiel@email.unc.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/2025/08/PXD042550

PRIDE project URI

• PRIDE
  1. PXD042550
     1. Label: PRIDE project
     2. Name: Persistent Type I Interferon Signaling in the Brain of People with HIV under ART with Cognitive Impairment