Evidence map›Paper›PMID 41529060›Full record

ArticlePLoS pathogens2026

Development and validation of HIV SMRTcap for the characterization of HIV-1 reservoirs across tissues and subtypes.

Ghazal Sadri, Steven T Nadakal, William Lauer, Justin Kos, Parmit K Singh, Erin Elliott, Catherine W Kaiser, Easton E Ford, Nadia Richardson, Kaitlyn M Shields and 25 more

Abstract read
In one paragraph

Article in PLoS pathogens, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

35 authors.

Ghazal SadriDepartment of Biochemistry and Molecular Genetics, University of Louisville, Louisville, Kentucky, United States of America.
Steven T NadakalDepartment of Biochemistry and Molecular Genetics, University of Louisville, Louisville, Kentucky, United States of America.
William LauerDepartment of Biochemistry and Molecular Genetics, University of Louisville, Louisville, Kentucky, United States of America.
Justin KosDepartment of Biochemistry and Molecular Genetics, University of Louisville, Louisville, Kentucky, United States of America.
Parmit K SinghDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
Erin ElliottDepartment of Biochemistry and Molecular Genetics, University of Louisville, Louisville, Kentucky, United States of America.
Catherine W KaiserDepartment of Biochemistry and Molecular Genetics, University of Louisville, Louisville, Kentucky, United States of America.
Easton E FordDepartment of Biochemistry and Molecular Genetics, University of Louisville, Louisville, Kentucky, United States of America.
Nadia RichardsonDepartment of Biochemistry and Molecular Genetics, University of Louisville, Louisville, Kentucky, United States of America.
Kaitlyn M ShieldsDepartment of Biochemistry and Molecular Genetics, University of Louisville, Louisville, Kentucky, United States of America.
Elizabeth HudsonDepartment of Biochemistry and Molecular Genetics, University of Louisville, Louisville, Kentucky, United States of America.
Noemi L LindenDepartment of Medicine, Division of Infectious Diseases, Weill Cornell Medicine, New York, New York, United States of America.
Ali DaneshDepartment of Microbiology and Immunology, Weill Cornell Medicine, New York, New York, United States of America.
James PowellDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
Peter WarburtonDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
Juan SotoDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
Matthew EmeryDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
Gintaras DeikusDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
Guinevere Q LeeDepartment of Medicine, Division of Infectious Diseases, Weill Cornell Medicine, New York, New York, United States of America.
Susanna L LamersBioinfoExperts, LLC., Thibodaux, Louisiana, United States of America.
Steven J ReynoldsRakai Health Sciences Program, Kalisizo, Uganda.
Ronald GaliwangoRakai Health Sciences Program, Kalisizo, Uganda.
Jessica L ProdgerDepartment of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
Stephen TomusangeRakai Health Sciences Program, Kalisizo, Uganda.
Taddeo KityamuweesiRakai Health Sciences Program, Kalisizo, Uganda.
Tina HanTwist Bioscience Corp., San Francisco, California, United States of America.
R Brad JonesDepartment of Microbiology and Immunology, Weill Cornell Medicine, New York, New York, United States of America.
Aaron A R TobianDepartment of Pathology, Johns Hopkins University, Baltimore, Maryland, United States of America.
Alan N EngelmanDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
Robert SebraDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
Susan MorgelloDivision of Neuro-Infectious Diseases, Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
Andrew D ReddLaboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Baltimore, Maryland, United States of America.
David SachsDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
Eric RouchkaDepartment of Biochemistry and Molecular Genetics, University of Louisville, Louisville, Kentucky, United States of America.
Melissa L SmithDepartment of Biochemistry and Molecular Genetics, University of Louisville, Louisville, Kentucky, United States of America.ORCID https://orcid.org/0000-0001-7151-3207

Funding

WKU Lead Faculty AwardP20GM103436 · NIGMS · UNIVERSITY OF LOUISVILLE · PI ERIC C ROUCHKA · 2012 to 2026
$60.1M
REACH: Research Enterprise to Advance a Cure for HIVUM1AI164565 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI Marina Caskey, R. Brad Jones · 2021 to 2026
$32.9M
Project 3. IntegrationU54AI170791 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI ANGELA M. GRONENBORN, Tatyana Polenova · 2022 to 2026
$30.6M
The Manhattan HIV Brain BankU24MH100931 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI MORGELLO, SUSAN · 2013 to 2023
$14.0M
Nuclear Localization of HIV-1 Preintegration ComplexesR01AI052014 · NIAID · DANA-FARBER CANCER INSTITUTE · PI ENGELMAN, ALAN N. · 2003 to 2025
$11.4M
THE NNTC COLLECTS, STORE, AND PROVIDE CLINICAL DATA AND WELL CHARACTERIZED BIOLOGICAL SPECIMENS, INCLUDING POST-MORTEM TISSUE FROM STUDY VOLUNTEERS AND/OR ORGAN DONORS WITH HIV AS WELL AS HIV-NEGATIVE75N95023C00015 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI HADIJAH, VACTOR · 2023 to 2025
$9.0M
T-cell depletion and maintenance of the HIV-1 latent reservoir in distinct tissue compartmentsR01DK131926 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI Melissa Laird Smith, AARON A TOBIAN · 2022 to 2026
$3.6M
Defining and then Maximizing the Footprint of CTL Selection on HIV Integration Site Landscapes to Optimize Cure StrategiesR37AI181626 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI Frederic D Bushman, R. Brad Jones · 2024 to 2026
$2.5M
Characterization of Non-subtype B HIV-1 Reservoirs and its Association with Longitudinal Clinical OutcomesR01AI162221 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI LEE, GUINEVERE · 2021 to 2025
$2.1M
Expanding regional capacity for single molecule sequencing through the purchase of the Sequel IIe sequencing systemS10OD034432 · OD · UNIVERSITY OF LOUISVILLE · PI SMITH, MELISSA LAIRD · 2023 to 2023
$484k
Characterization of clonal expansion in the CNS-restricted reservoir using HIV SMRTcap, a novel single molecule assay providing simultaneous resolution of proviral genomes and integration sitesR21MH122368 · NIMH · UNIVERSITY OF LOUISVILLE · PI SMITH, MELISSA LAIRD · 2020 to 2021
$428k
NIAID NIH HHS R01 AI052014NIAID NIH HHS R01 AI162221NIAID NIH HHS R37 AI181626NIAID NIH HHS U54 AI170791NIAID NIH HHS UM1 AI164565NIDA NIH HHS 75N95023C00015NIDDK NIH HHS R01 DK131926NIGMS NIH HHS P20 GM103436NIH HHS S10 OD034432NIMH NIH HHS R21 MH122368NIMH NIH HHS U24 MH100931
6 · The paper itself

Abstract

Human Immunodeficiency Virus type 1 (HIV-1) is responsible for the global HIV/AIDS epidemic and the establishment of an integrated HIV-1 reservoir remains the primary obstacle to cure. Upon therapy interruption, reactivation of the persistent HIV-1 reservoir propagates viral rebound and mediates continued immunological decline. While furthering understanding of the HIV-1 reservoir is essential for HIV-1 cure, commonly used sequencing strategies are often limited by the reliance on short-read sequencing across separate assays to determine integration sites and proviral integrity - something that does not always adequately resolve complex human genomic repeats or low complexity regions. Simultaneous identification of proviral integration sites and proviral integrity at the single molecule level would enable HIV-1 reservoir characterization with minimal imputation or bioinformatic reconstruction. Here we present HIV Single Molecule Real Time Capture (HIV SMRTcap), a novel molecular and computational pipeline that directly and simultaneously identifies HIV-1 integration sites, defines proviral integrity, and characterizes clonal expansion of HIV-1 provirus-containing cells with single molecule resolution. In combination with long-read, single-molecule, real-time (SMRT) sequencing and custom analytic pipelines, HIV SMRTcap enables a highly comprehensive characterization of HIV-1 reservoirs. Moreover, we demonstrate here that HIV SMRTcap performs robustly across the major global subtypes (HIV-1 subtype A, B, C, D and A/D recombinant viruses), and can use both cell- and tissue-derived inputs, including samples from antiretroviral therapy (ART) treated individuals with undetectable viral loads. Our results demonstrate that HIV SMRTcap serves as a comprehensive, robust method for unbiased HIV-1 reservoir characterization. Used alone, or in combination with single-cell based methods, HIV SMRTcap will enable novel exploration of viral reservoirs across subtypes and in tissue-specific compartments, providing critical information needed to inform HIV-1 cure.

Indexed as

HIV-1HIV InfectionsProvirusesVirus IntegrationHumansViral LoadVirus Latency

Identifiers

PMID41529060
PMCPMC12851485

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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.