Evidence map›Paper›PMID 41959410›Full record

ArticlebioRxiv : the preprint server for biology2026

Atlas of HIV cis-regulatory elements reveals extensive transcriptional variation across clades, isolates, and within individuals.

Berkay Engin, Mohamed Yousry ElSadec, Joseph Alexander Finkelberg, Tommy Henry Taslim, Daniel L Bryant, Luis Soto-Ugaldi, Susan Kales, Ching-Huang Ho, Maryam Dashtiahangar, George Muñoz-Esquivel and 11 more

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

21 authors.

Berkay EnginBoston University, Biology Department, Boston, MA, 02215, USA.
Mohamed Yousry ElSadecBioinformatics Program, Boston University, Boston, MA 02215, USA.
Joseph Alexander FinkelbergBioinformatics Program, Boston University, Boston, MA 02215, USA.
Tommy Henry TaslimMolecular Biology, Cell Biology and Biochemistry Program, Boston University, Boston, MA 02215, USA.
Daniel L BryantDepartment of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA.
Luis Soto-UgaldiTri-institutional Program, Computational Biology and Medicine, New York, NY 10065, USA.
Susan KalesThe Jackson Laboratory, Bar Harbor, ME 04609, USA.
Ching-Huang HoCenter for Systems Immunology, Benaroya Research Institute, Seattle WA 98101, USA.
Maryam DashtiahangarMolecular Biology, Cell Biology and Biochemistry Program, Boston University, Boston, MA 02215, USA.
George Muñoz-EsquivelEscuela Profesional de Genetica y Biotecnologia, Facultad de Ciencias Biológicas, Universidad Nacional Mayor de San Marcos, Lima 15081, Peru.
Elvis MoraraMolecular Biology, Cell Biology and Biochemistry Program, Boston University, Boston, MA 02215, USA.
Jacob PurintonMolecular Biology, Cell Biology and Biochemistry Program, Boston University, Boston, MA 02215, USA.
Benedetta D'EliaMolecular Biology, Cell Biology and Biochemistry Program, Boston University, Boston, MA 02215, USA.
Rodrigo CastroThe Jackson Laboratory, Bar Harbor, ME 04609, USA.
Harshpreet ChandokThe Jackson Laboratory, Bar Harbor, ME 04609, USA.
Matias Alejandro PazMolecular Biology, Cell Biology and Biochemistry Program, Boston University, Boston, MA 02215, USA.
Trevor SiggersBoston University, Biology Department, Boston, MA, 02215, USA.ORCID 0000-0002-8039-7639
John P RayCenter for Systems Immunology, Benaroya Research Institute, Seattle WA 98101, USA.
Andrew J HendersonDepartment of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA.
Ryan TewheyThe Jackson Laboratory, Bar Harbor, ME 04609, USA.ORCID 0000-0002-4607-8001
Juan I Fuxman BassBoston University, Biology Department, Boston, MA, 02215, USA.

Funding

Translational ScienceP30AI042853 · NIAID · MIRIAM HOSPITAL · PI CURT G BECKWITH, DEBBIE M. CHENG · 1998 to 2026
$51.7M
BU Clinical HIV/AIDS Research Training Program (BU-CHART)T32AI052074 · NIAID · BOSTON UNIVERSITY MEDICAL CAMPUS · PI Benjamin P. Linas · 2003 to 2026
$6.7M
T cells promoting transitions toward autoimmunityU01AI176320 · NIAID · BENAROYA RESEARCH INST AT VIRGINIA MASON · PI Jane Hoyt Buckner, S Alice Long · 2023 to 2026
$4.7M
Structure and Function of Immune Gene Regulatory NetworksR35GM128625 · NIGMS · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI Juan Ignacio Fuxman Bass · 2018 to 2026
$4.0M
Persistent HIV-1 expression and microglia dysfunctionR01DA055488 · NIDA · BOSTON MEDICAL CENTER · PI GUMMULURU, SURYARAM, HENDERSON, ANDREW J · 2021 to 2025
$3.7M
Biophysical and functional characterization of immune-related regulatory elements and noncoding variantsR01AI151051 · NIAID · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI SIGGERS, TREVOR · 2020 to 2024
$2.8M
Investigating Genetic and Epigenetic Control of T Cell Function in AutoimmunityDP2AI183504 · NIAID · BENAROYA RESEARCH INST AT VIRGINIA MASON · PI John Philip Ray · 2023 to 2026
$2.6M
Functional Mapping of Enhancer Conservation Between Species to Enable Mechanistic Insights into Polygenic DiseaseR35HG011329 · NHGRI · JACKSON LABORATORY · PI TEWHEY, RYAN · 2021 to 2025
$2.6M
Defective HIV proviruses and Persistent Innate Immune ActivationR01AI187175 · NIAID · BOSTON MEDICAL CENTER · PI SURYARAM GUMMULURU, Andrew J Henderson · 2024 to 2026
$2.4M
Genetic variants guiding pathogenicity of colitogenic T cellsR01DK140972 · NIDDK · BENAROYA RESEARCH INST AT VIRGINIA MASON · PI Oliver James Harrison, John Philip Ray · 2024 to 2026
$1.5M
Predoctoral Training in Bioinformatics and Computational BiologyT32GM150533 · NIGMS · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI GARY E. BENSON, Daniel Segre · 2023 to 2026
$1.3M
Synthetic Biology and Biotechnology (SB2) Predoctoral Training ProgramT32GM154655 · NIGMS · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI CHRISTOPHER S CHEN, Ahmad Samir Khalil · 2025 to 2026
$858k
NHGRI NIH HHS R35 HG011329NIAID NIH HHS DP2 AI183504NIAID NIH HHS P30 AI042853NIAID NIH HHS R01 AI151051NIAID NIH HHS R01 AI187175NIAID NIH HHS T32 AI052074NIAID NIH HHS U01 AI176320NIDA NIH HHS R01 DA055488NIDDK NIH HHS R01 DK140972NIGMS NIH HHS R35 GM128625NIGMS NIH HHS T32 GM150533NIGMS NIH HHS T32 GM154655
6 · The paper itself

Abstract

Human immunodeficiency virus (HIV) replication, persistence, and reactivation depend on transcription from integrated proviruses. Despite extensive sequence variation, how viral genetic diversity influences transcriptional regulation remains poorly understood. Here, we generate a functional regulatory atlas of HIV-1 and HIV-2 by combining tiling and saturation mutagenesis massively parallel reporter assays (MPRAs) with comparative sequence analysis and predictive modeling. By profiling thousands of HIV isolates in Jurkat and human primary CD4+T cells, we reveal extensive variation in baseline and stimulus-induced long terminal repeat (LTR) activity across and within clades, driven by distinct transcription factor configurations. These activities frequently differ among proviruses from the same individual and shift over infection and transmission without consistent selection for activity. Beyond the LTR, we identify conserved intragenic cis-regulatory elements, revealing regulatory architectures that complement LTR activity. Finally, we develop sequence-based models that accurately predict transcriptional activity, enabling scalable functional annotation of viral diversity and evolution.

Identifiers

PMID41959410
PMCPMC13060177

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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.