Evidence map›Paper›PMID 42013838›Full record

ArticleCell2026

Systematic discovery of pro- and anti-HIV host factors in primary human CD4+ T cells.

Ujjwal Rathore, Eli Dugan, Hunter Thornton, Vigneshwari Easwar Kumar, Rama Dajani, Ryan C Burdick, Janet M Young, Zachary Steinhart, Reanna Lao, Krista A Delviks-Frankenberry and 28 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

38 authors.

Ujjwal RathoreGladstone Institutes, San Francisco, CA, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA. Electronic address: ujjwal.rathore@gladstone.ucsf.edu.
Eli DuganGladstone Institutes, San Francisco, CA, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA; Tetrad Graduate Program, University of California, San Francisco, San Francisco, CA, USA.
Hunter ThorntonGladstone Institutes, San Francisco, CA, USA.
Vigneshwari Easwar KumarGladstone Institutes, San Francisco, CA, USA.
Rama DajaniGladstone Institutes, San Francisco, CA, USA.
Ryan C BurdickViral Mutation Section, HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA.
Janet M YoungDivision of Basic Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Zachary SteinhartGladstone Institutes, San Francisco, CA, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Reanna LaoGladstone Institutes, San Francisco, CA, USA; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA.
Krista A Delviks-FrankenberryViral Mutation Section, HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA.
Wooyoung ChoiDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.
William S HenriquesDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA; Department of Cellular & Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA.
Ignacia EcheverriaQuantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.
Emma DannGladstone Institutes, San Francisco, CA, USA; Department of Genetics, Stanford University, Stanford, CA, USA.
Ishaan DurejaGladstone Institutes, San Francisco, CA, USA.
Nandini PathakGladstone Institutes, San Francisco, CA, USA.
Maya M ArceGladstone Institutes, San Francisco, CA, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Justin McKetneyGladstone Institutes, San Francisco, CA, USA; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA.
Jennifer M UmhoeferGladstone Institutes, San Francisco, CA, USA.
Simrun ParulekarGladstone Institutes, San Francisco, CA, USA.
Ralf SchmidtGladstone Institutes, San Francisco, CA, USA; Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
Benjamin J PolaccoGladstone Institutes, San Francisco, CA, USA; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA.
Jason NeidlemanGladstone Institutes, San Francisco, CA, USA.
Mauricio MontanoGladstone Institutes, San Francisco, CA, USA.
Vinh Q NguyenGladstone Institutes, San Francisco, CA, USA; Department of Surgery, University of California, San Francisco, San Francisco, CA, USA.
Andrej SaliQuantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.
Jay A LevyDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Jeannette L TenthoreyDepartment of Cellular & Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA.
Yifan ChengDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA, USA.
Nadia R RoanGladstone Institutes, San Francisco, CA, USA; Department of Urology, University of California, San Francisco, San Francisco, CA, USA.
Danielle L SwaneyGladstone Institutes, San Francisco, CA, USA; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.
Robyn M KaakeGladstone Institutes, San Francisco, CA, USA; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.
Stacie E DodgsonGladstone Institutes, San Francisco, CA, USA.
Joseph HiattGladstone Institutes, San Francisco, CA, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Vinay K PathakViral Mutation Section, HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA.
Harmit S MalikDivision of Basic Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA; Howard Hughes Medical Institute, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Nevan J KroganGladstone Institutes, San Francisco, CA, USA; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.
Alexander MarsonGladstone Institutes, San Francisco, CA, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA; Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA. Electronic address: alexander.marson@ucsf.edu.

Funding

Project 3U54AI170792 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Nevan J Krogan · 2022 to 2026
$35.7M
CHEETAH Center for the Structural Biology of HIV Infection, Restriction, and Viral DynamicsU54AI170856 · NIAID · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI WALTHER H MOTHES · 2022 to 2026
$34.4M
Research BaseP30DK063720 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VAISSE, CHRISTIAN · 2003 to 2019
$21.8M
Tetrad: Genetics, Cell Biology, Biochemistry and Molecular Biology Training GrantT32GM139786 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Natalia Jura, David Paul Toczyski · 2021 to 2026
$6.5M
Restorative practice in repairing harm and promoting safe and inclusive practices in the laboratory.T32GM136547 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Adrian Erlebacher, Anita Sil · 2020 to 2026
$4.5M
Phenotypic and mechanistic analysis of the in vivo HIV latent reservoir by single-cell technologiesR01AI147777 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ROAN, NADIA R · 2019 to 2022
$3.8M
Multiomics characterization, induction, and elimination of the HIV gut reservoirR01DK131526 · NIDDK · J. DAVID GLADSTONE INSTITUTES · PI Nancie Marie Archin, Nadia R Roan · 2022 to 2026
$3.7M
Targeting the transcriptionally-active reservoir to reduce chronic inflammation in aged people with HIVR01AI183286 · NIAID · J. DAVID GLADSTONE INSTITUTES · PI Melanie Maria Ott, Nadia R Roan · 2024 to 2026
$2.7M
Functional Testing of Host Genes that Control HIV Latency in Primary Immune CellsDP2DA042423 · NIDA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MARSON, ALEXANDER · 2016 to 2016
$2.4M
Using in vivo genetic and physical interaction data for structure determination of protein assembliesR35GM151256 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Ignacia Echeverria Riesco · 2023 to 2026
$1.6M
Illumina NovaSeq 6000 Sequencing SystemS10OD028511 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHOW, ERIC D · 2020 to 2020
$583k
BD FACSAria Fusion Cell SorterS10OD021822 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LEE, MICHAEL R. · 2016 to 2016
$573k
NCRR NIH HHS S10 RR028962NIAID NIH HHS R01 AI147777NIAID NIH HHS R01 AI183286NIAID NIH HHS U54 AI170792NIAID NIH HHS U54 AI170856NIDA NIH HHS DP2 DA042423NIDDK NIH HHS P30 DK063720NIDDK NIH HHS R01 DK131526NIGMS NIH HHS R35 GM151256NIGMS NIH HHS T32 GM136547NIGMS NIH HHS T32 GM139786NIH HHS S10 OD021822NIH HHS S10 OD028511
6 · The paper itself

Abstract

Host factors that promote or restrict human immunodeficiency virus (HIV) infection in human CD4+ T cells have not been comprehensively identified. We employed orthogonal genome-wide CRISPR activation (CRISPRa) and CRISPR knockout screens in primary CD4+ T cells to discover pro- and anti-HIV host factors systematically. Secondary pooled screens and individual perturbations validated high-confidence hits and revealed diverse mechanisms of action. CRISPRa uncovered multiple potent antiviral factors, including PI16, PPID, SHISA3, and ITM2A. PI16 interacts with host factors involved in HIV fusion and inhibits viral entry, whereas PPID (Cyp40), a paralog of the proviral cyclophilin CypA, binds capsid and reduces nuclear import of the HIV core. Structural modeling, evolutionary analyses, and targeted mutagenesis revealed domains and residues required for PPID-mediated HIV restriction, including non-human primate ortholog substitutions that enhance antiviral activity. Together, these data define the functional HIV-host interaction landscape in primary human T cells and uncover new mechanisms modulating infection.

Indexed as

CD4-Positive T-LymphocytesHIV-1HIV InfectionsHost-Pathogen InteractionsHumansCRISPRHIV-1HIV-host interactionshuman T cellsimmunologypooled screensvirology

Identifiers

PMID42013838
PMCPMC13105272

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.