Evidence map›Paper›PMID 35801589›Full record

ArticleJCI insight2022

HIV viral transcription and immune perturbations in the CNS of people with HIV despite ART.

Shelli F Farhadian, Ofir Lindenbaum, Jun Zhao, Michael J Corley, Yunju Im, Hannah Walsh, Alyssa Vecchio, Rolando Garcia-Milian, Jennifer Chiarella, Michelle Chintanaphol and 8 more

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 1 pooled it
2.6field-weighted citation impact, top 8% of its field
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

30 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.

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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

18 authors at 5 institutions in 1 country.

Shelli F FarhadianDepartment of Medicine, Section of Infectious Diseases, and.
Ofir LindenbaumProgram in Applied Mathematics, and.
Jun ZhaoInterdepartmental Program in Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut, USA.
Michael J CorleyDepartment of Medicine, Division of Infectious Diseases, and.
Yunju ImDepartment of Biostatistics, Yale School of Public Health, New Haven, Connecticut, USA.
Hannah WalshDepartment of Medicine, Section of Infectious Diseases, and.
Alyssa VecchioUniversity of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA.
Rolando Garcia-MilianBioinformatics Support Program, Cushing/Whitney Medical Library, Yale School of Medicine, New Haven, Connecticut, USA.
Jennifer ChiarellaDepartment of Neurology, Yale School of Medicine, New Haven, Connecticut, USA.
Michelle ChintanapholDepartment of Neurology, Yale School of Medicine, New Haven, Connecticut, USA.
Rachela CalviDepartment of Neurology, Yale School of Medicine, New Haven, Connecticut, USA.
Guilin WangYale Center for Genome Analysis, Yale University, New Haven, Connecticut, USA.
Lishomwa C NdhlovuDepartment of Medicine, Division of Infectious Diseases, and.
Jennifer YoonDepartment of Medicine, Section of Infectious Diseases, and.
Diane TrottaDepartment of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA.
Shuangge MaDepartment of Biostatistics, Yale School of Public Health, New Haven, Connecticut, USA.
Yuval KlugerProgram in Applied Mathematics, and.
Serena SpudichDepartment of Neurology, Yale School of Medicine, New Haven, Connecticut, USA.
Yale University · USCornell University · USOffice of Infectious Diseases · USUniversity of North Carolina at Chapel Hill · USWhitney Museum of American Art · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Yale Study Support Suite (YES3): Dashboard and Web Portal Software Supporting Research Workflow through integrated, customizable REDCap External ModulesP30AG021342 · NIA · YALE UNIVERSITY · PI Albert C Shaw · 2002 to 2026
$37.9M
HOPE - HIV Obstruction by Programmed EpigeneticsUM1AI164559 · NIAID · J. DAVID GLADSTONE INSTITUTES · PI Lishomwa C Ndhlovu, Melanie Maria Ott · 2021 to 2026
$32.2M
Yale Training Program in Geriatric Clinical Epidemiology and Aging-Related ResearchT32AG019134 · NIA · YALE UNIVERSITY · PI Terri R. Fried · 2001 to 2026
$7.5M
CNS Viral Persistence and Neuropsychiatric Perturbations in HIV: Single cell and Molecular InterrogationR01MH125737 · NIMH · YALE UNIVERSITY · PI CYKTOR, JOSHUA CHARLES, SPUDICH, SERENA S · 2021 to 2025
$5.4M
Harnessing Single Cell Epigenome-wide profiling of Myeloid cells to Compare and Contrast Alzheimer's from HIV-Associated Cognitive DysfunctionR01AG063846 · NIA · WEILL MEDICAL COLL OF CORNELL UNIV · PI NDHLOVU, LISHOMWA C, VALCOUR, VICTOR · 2020 to 2024
$4.4M
Integrative Single Cell isoform and chromatin accessibility Mapping of Chronic Opioid Exposure in Cognitive Brain Areas in HIVU01DA053625 · NIDA · WEILL MEDICAL COLL OF CORNELL UNIV · PI MILNER, TERESA A, NDHLOVU, LISHOMWA C · 2021 to 2025
$4.0M
Investigating Cellular Immunometabolic Mechanisms Underlying HIV-Related Cardiovascular Disease RiskR01HL160392 · NHLBI · WEILL MEDICAL COLL OF CORNELL UNIV · PI CORLEY, MICHAEL JAY · 2021 to 2024
$2.3M
EFFICIENT METHODS FOR CALIBRATION, CLUSTERING, VISUALIZATION AND IMPUTATION OF LARGE scRNA-seq DATAR01GM131642 · NIGMS · YALE UNIVERSITY · PI KLUGER, YUVAL · 2019 to 2022
$1.6M
The role of epigenetic transcriptional memory in monocyte-macrophage cells and cardiovascular disease riskK01HL140271 · NHLBI · WEILL MEDICAL COLL OF CORNELL UNIV · PI CORLEY, MICHAEL JAY · 2018 to 2022
$788k
Understanding the cellular basis for persistent immune activation in the central nervous system during virologically suppressed HIVK23MH118999 · NIMH · YALE UNIVERSITY · PI FARHADIAN, SHELLI · 2018 to 2021
$770k
Single cell RNAseq of CSF to Dissect CNS Cellular Perturbations in Long-term Treated HIVR21MH118109 · NIMH · YALE UNIVERSITY · PI SPUDICH, SERENA S · 2018 to 2019
$461k
NCATS NIH HHS UL1 TR001863NHLBI NIH HHS K01 HL140271NHLBI NIH HHS R01 HL160392NIAID NIH HHS UM1 AI164559NIA NIH HHS P30 AG021342NIA NIH HHS R01 AG063846NIA NIH HHS T32 AG019134NIDA NIH HHS U01 DA053625NIGMS NIH HHS R01 GM131642NIMH NIH HHS K23 MH118999NIMH NIH HHS R01 MH125737NIMH NIH HHS R21 MH118109
6 · The paper itself

Abstract

People with HIV (PWH) on antiretroviral therapy (ART) experience elevated rates of neurological impairment, despite controlling for demographic factors and comorbidities, suggesting viral or neuroimmune etiologies for these deficits. Here, we apply multimodal and cross-compartmental single-cell analyses of paired cerebrospinal fluid (CSF) and peripheral blood in PWH and uninfected controls. We demonstrate that a subset of central memory CD4+ T cells in the CSF produced HIV-1 RNA, despite apparent systemic viral suppression, and that HIV-1-infected cells were more frequently found in the CSF than in the blood. Using cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq), we show that the cell surface marker CD204 is a reliable marker for rare microglia-like cells in the CSF, which have been implicated in HIV neuropathogenesis, but which we did not find to contain HIV transcripts. Through a feature selection method for supervised deep learning of single-cell transcriptomes, we find that abnormal CD8+ T cell activation, rather than CD4+ T cell abnormalities, predominated in the CSF of PWH compared with controls. Overall, these findings suggest ongoing CNS viral persistence and compartmentalized CNS neuroimmune effects of HIV infection during ART and demonstrate the power of single-cell studies of CSF to better understand the CNS reservoir during HIV infection.

Indexed as

HIV-1HIV InfectionsHumansLongitudinal StudiesMicrogliaViral TranscriptionAIDS/HIVNeurological disordersNeuroscience

Identifiers

PMID35801589
PMCPMC9310520
OpenAlexW4284699944

What OpenQuestion holds

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LicenceCC BY
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.