Evidence map›Paper›PMID 31779701›Full record

ArticleHuman genomics2019

Transcriptomic analysis of monocytes from HIV-positive men on antiretroviral therapy reveals effects of tobacco smoking on interferon and stress response systems associated with depressive symptoms.

David R Lorenz, Vikas Misra, Dana Gabuzda

Open access · goldAbstract read
In one paragraph

Article in Human genomics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
0.7field-weighted citation impact, top 36% 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

13 citing papers in PubMed, 16 citations in OpenAlex.

  1. Trial
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  4. Review
  5. Fibroblast-Mediated Macrophage Recruitment Supports Acute Wound Healing.The Journal of investigative dermatology · 2025
    Article
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  13. Risk Factors for Depression Among Middle-Aged to Older People Living With HIV in Lima, Peru.Journal of the International Association of Providers of AIDS Care
    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

3 authors at 1 institution in 1 country.

David R LorenzDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Center for Life Science 1010, 450 Brookline Avenue, Boston, MA, 02215, USA.
Vikas MisraDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Center for Life Science 1010, 450 Brookline Avenue, Boston, MA, 02215, USA.
Dana GabuzdaDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Center for Life Science 1010, 450 Brookline Avenue, Boston, MA, 02215, USA. dana_gabuzda@dfci.harvard.edu.ORCID 0000-0002-4964-5083
Dana-Farber Cancer Institute · US

Funding

NATURAL HISTORY OF AIDS IN HOMOSEXUAL MENU01AI035040 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DETELS, ROGER, MARTINEZ-MAZA, OTONIEL · 1993 to 2018
$75.2M
University of Pittsburgh Multicenter AIDS Cohort Study (MACS)U01AI035041 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MARTINSON, JEREMY JAMES, RINALDO, CHARLES R · 1993 to 2018
$71.4M
MULTICENTER AIDS COHORT STUDYU01AI035039 · NIAID · NORTHWESTERN UNIVERSITY AT CHICAGO · PI WOLINSKY, STEVEN M · 1993 to 2018
$66.4M
Multicenter Aids Cohort Study- Part B (Baltimore Site)U01AI035042 · NIAID · JOHNS HOPKINS UNIVERSITY · PI BROWN, TODD T, MARGOLICK, JOSEPH B. · 1993 to 2018
$61.5M
Clinical Research Sites for the MACS/WIHS Combined Cohort Study (MACS/WIHS-CCS) - Baltimore/Wash DC Center - Admin Supplement: Vision and dual sensory loss in HIV-infected older adultsU01HL146201 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI TODD T BROWN, Joseph B. Margolick · 2019 to 2026
$33.7M
METHODOLOGICAL EXPERTISE IN INTREPRETING MACS DATAU01AI035043 · NIAID · JOHNS HOPKINS UNIVERSITY · PI JACOBSON, LISA P · 1993 to 2011
$26.9M
Institute for Clinical and Translational ResearchUL1TR000424 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2012 to 2012
$6.0M
Effects of marijuana use on inflammation and vascular injury in adults with HIV infectionR01DA046203 · NIDA · DANA-FARBER CANCER INST · PI GABUZDA, DANA H. · 2018 to 2022
$3.2M
Stress response networks in HIV infectionR01DA040391 · NIDA · DANA-FARBER CANCER INST · PI GABUZDA, DANA H. · 2015 to 2019
$2.2M
Neuroimmune mechanisms of depression in adults with HIV infectionR01MH110259 · NIMH · DANA-FARBER CANCER INST · PI GABUZDA, DANA H. · 2016 to 2020
$1.8M
Pathways to HIV-Associated Neurocognitive Disorders: A Systems Biology ApproachR01DA030913 · NIDA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HORVATH, STEVE, LEVINE, ANDREW J · 2010 to 2014
$1.5M
NCATS NIH HHS UL1 TR000424NHLBI NIH HHS U01 HL146201NIAID NIH HHS U01 AI035039NIAID NIH HHS U01 AI035041NIAID NIH HHS U01 AI035042NIAID NIH HHS U01 AI035043NIDA NIH HHS R01 DA040391NIDA NIH HHS R01 DA046203NIH HHS DA046203NIH HHS DA40391NIH HHS MH110259NIMH NIH HHS R01 MH110259
6 · The paper itself

Abstract

backgroundTobacco smoking induces immunomodulatory and pro-inflammatory effects associated with transcriptome changes in monocytes and other immune cell types. While smoking is prevalent in HIV-infected (HIV+) individuals, few studies have investigated its effects on gene expression in this population. Here, we report whole-transcriptome analyses of 125 peripheral blood monocyte samples from ART-treated HIV+ and uninfected (HIV-) men enrolled in the Multicenter AIDS Cohort Study (MACS) (n = 25 HIV+ smokers, n = 60 HIV+ non-smokers, n = 40 HIV- non-smoking controls). Gene expression profiling was performed using Illumina HumanHT-12 Expression BeadChip microarrays. Differential expression analysis was performed with weighted linear regression models using the R limma package, followed by functional enrichment and Ingenuity Pathway analyses.

resultsA total of 286 genes were differentially expressed in monocytes from HIV+ smokers compared with HIV- non-smokers; upregulated genes (n = 180) were enriched for immune and interferon response, chemical/stress response, mitochondria, and extracellular vesicle gene ontology (GO) terms. Expression of genes related to immune/interferon responses (AIM2, FCGR1A-B, IFI16, SP100), stress/chemical responses (APAF1, HSPD1, KLF4), and mitochondrial function (CISD1, MTHFD2, SQOR) was upregulated in HIV+ non-smokers and further increased in HIV+ smokers. Gene expression changes associated with smoking in previous studies of human monocytes were also observed (SASH1, STAB1, PID1, MMP25). Depressive symptoms (CES-D scores ≥ 16) were more prevalent in HIV+ tobacco smokers compared with HIV+ and HIV- non-smokers (50% vs. 26% and 13%, respectively; p = 0.007), and upregulation of immune/interferon response genes, including IFI35, IFNAR1, OAS1-2, STAT1, and SP100, was associated with depressive symptoms in logistic regression models adjusted for HIV status and smoking (p < 0.05). Network models linked the Stat1-mediated interferon pathway to transcriptional regulator Klf4 and smoking-associated toll-like receptor scaffolding protein Sash1, suggesting inter-relationships between smoking-associated genes, control of monocyte differentiation, and interferon-mediated inflammatory responses.

conclusionsThis study characterizes immune, interferon, stress response, and mitochondrial-associated gene expression changes in monocytes from HIV+ tobacco smokers, and identifies augmented interferon and stress responses associated with depressive symptoms. These findings help to explain complex interrelationships between pro-inflammatory effects of HIV and smoking, and their combined impact on comorbidities prevalent in HIV+ individuals.

Indexed as

Antiretroviral Therapy, Highly ActiveGene Expression ProfilingAdultAgedDepressionGene Expression RegulationGene OntologyGene Regulatory NetworksHIV InfectionsHIV SeropositivityHumansInterferonsKruppel-Like Factor 4MaleMiddle AgedSignal TransductionInterferonsKLF4 protein, humanKruppel-Like Factor 4DepressionHIVImmune responseInterferon responseMitochondriaMonocytesSmokingStress responseTobaccoTranscriptomics

Identifiers

PMID31779701
PMCPMC6883692
OpenAlexW2991201477

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.