PXD071892

PXD071892 is an original dataset announced via ProteomeXchange.

Title	Systematic Discovery of Pro- and Anti-HIV Host Factors in Primary Human CD4+ T Cells
Description	Despite extensive efforts, significant gaps remain in our understanding of which host factors promote or restrict human immunodeficiency virus (HIV) infection in human CD4+ T cells. Here, we employed orthogonal genome-wide CRISPR activation (CRISPRa) and CRISPR knockout (CRISPRn) screens in primary CD4+ T cells to discover both pro- and anti-HIV host factors systematically. We used secondary pooled screens and targeted individual CRISPR perturbations to validate high-confidence hits and reveal their diverse mechanisms of action. CRISPRa notably revealed potent antiviral factors, including PI16, PPID, SHISA3, and ITM2A – many of which would have been missed by gene knockout experiments alone. When PI16 is overexpressed in CD4+ T cells, it physically interacts with CD4 and numerous HIV host factors involved in viral fusion, and efficiently inhibits HIV entry. We also discovered another novel antiviral factor, PPID (Cyp40). PPID is a paralog of CypA (or PPIA), which is a proviral factor that regulates nuclear entry kinetics of HIV cores. PPID also binds to HIV capsid, but unlike CypA, it restricts infection by blocking nuclear import of the viral core. Structural modeling, evolutionary analyses, and targeted mutagenesis identified domains and residues that mediate restriction of HIV by PPID, including specific substitutions from non-human primate orthologs that improve HIV restriction. Together, our data systematically define the functional HIV-host interaction landscape in primary human T cells and reveal new mechanisms to modulate infection.
HostingRepository	PRIDE
AnnounceDate	2026-04-27
AnnouncementXML	Submission_2026-04-26_16:22:26.611.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Robyn Kaake
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-12-11 15:34:50	ID requested
⏵ 1	2026-04-26 16:22:27	announced

10.1016/j.cell.2026.03.046;

Rathore U, Dugan E, Thornton H, Kumar VE, Dajani R, Burdick RC, Young JM, Steinhart Z, Lao R, Delviks-Frankenberry KA, Choi W, Henriques WS, Echeverria I, Dann E, Dureja I, Pathak N, Arce MM, McKetney J, Umhoefer JM, Parulekar S, Schmidt R, Polacco BJ, Neidleman J, Montano M, Nguyen VQ, Sali A, Levy JA, Tenthorey JL, Cheng Y, Roan NR, Swaney DL, Kaake RM, Dodgson SE, Hiatt J, Pathak VK, Malik HS, Krogan NJ, Marson A, Systematic discovery of pro- and anti-HIV host factors in primary human CD4+ T cells. Cell, ():(2026) [pubmed]

submitter keyword: host factor,IP-MS, PPI, PI16, HIV, CD4+ T cells

Alexander Marson
contact affiliation	Gladstone Institure for Immunology; The J David Gladstone Institutes; San Francisco, CA, USA
contact email	alexander.marson@ucsf.edu
lab head
Robyn Kaake
contact affiliation	Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA
contact email	robyn.kaake@gladstone.ucsf.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/2026/04/PXD071892

PRIDE project URI

• PRIDE
  1. PXD071892
     1. Label: PRIDE project
     2. Name: Systematic Discovery of Pro- and Anti-HIV Host Factors in Primary Human CD4+ T Cells