Evidence map›Paper›PMID 32526847›Full record

ArticleCells2020

HIV Nef and Antiretroviral Therapy Have an Inhibitory Effect on Autophagy in Human Astrocytes that May Contribute to HIV-Associated Neurocognitive Disorders.

Laura Cheney, Hillary Guzik, Frank P Macaluso, Fernando Macian, Ana Maria Cuervo, Joan W Berman

Open access · goldAbstract read
In one paragraph

Article in Cells, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
2.6field-weighted citation impact, top 9% 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, 33 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Review
  6. Review
  7. Review
  8. Article
  9. Article
  10. HIV Protein Nef Induces Cardiomyopathy Through Induction of Bcl2 and p21.International journal of molecular sciences · 2024
    Article
  11. Review
  12. The role of autophagy in the progression of HIV infected cardiomyopathy.Frontiers in cell and developmental biology · 2024
    Review
  13. Review
  14. Article
  15. Neuro-HIV-New insights into pathogenesis and emerging therapeutic targets.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023
    Article
  16. Role of Dysregulated Autophagy in HIV Tat, Cocaine, and cART Mediated NLRP3 Activation in Microglia.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2023
    Article
  17. Review
  18. Article
  19. Article
  20. Review
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

6 authors at 1 institution in 1 country.

Laura CheneyDepartment of Medicine, Division of Infectious Diseases, Montefiore Medical Center and Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, USA.ORCID 0000-0003-3794-5289
Hillary GuzikAnalytical Imaging Facility, Montefiore Medical Center and Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, USA.ORCID 0000-0003-4655-8280
Frank P MacalusoAnalytical Imaging Facility, Montefiore Medical Center and Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, USA.
Fernando MacianDepartment of Pathology, Montefiore Medical Center and Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, USA.
Ana Maria CuervoDepartment of Developmental and Molecular Biology, Montefiore Medical Center and Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, USA.
Joan W BermanDepartment of Pathology, Montefiore Medical Center and Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, USA.
Albert Einstein College of Medicine · US

Funding

WORD PROCESSORP30CA013330 · NCI · YESHIVA UNIVERSITY · PI STEVEN C. ALMO · 1985 to 2026
$111.2M
Role of Autophagy in T Cell Function and Immunosenescence (Project 3)P01AG031782 · NIA · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI CUERVO, ANA MARIA · 2009 to 2024
$36.2M
Patient and Population Health Outcomes Research SWGP30AI124414 · NIAID · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI Kathryn M. Anastos · 2017 to 2026
$28.3M
Project 3: Autophagy dysfunction and neuronal activity in FTDU54NS100717 · NINDS · WEILL MEDICAL COLL OF CORNELL UNIV · PI GAN, LI · 2016 to 2020
$10.8M
Einstein's Nathan Shock Center of Excellence in Basic Biology of AgingP30AG038072 · NIA · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI HUFFMAN, DEREK MAJOR · 2010 to 2024
$10.8M
Geographic Medicine and Emerging InfectionsT32AI070117 · NIAID · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI WEISS, LOUIS M. · 2008 to 2023
$5.1M
Decreased Protein Degradation in AgingR37AG021904 · NIA · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI CUERVO, ANA MARIA · 2013 to 2022
$4.4M
Mechanisms of opioid- mediated HIV neuropathogenesisR01DA048609 · NIDA · ALBERT EINSTEIN COLLEGE OF MEDICINE · PI BERMAN, JOAN WEINBERGER, GOLDSTEIN, HARRIS · 2019 to 2023
$4.2M
Impact of illicit drugs, HIV, and ART on neuroinflammation and BBB disruptionR01DA044584 · NIDA · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI BERMAN, JOAN WEINBERGER, GOLDSTEIN, HARRIS · 2017 to 2021
$4.0M
Monocyte CNS HIV entry & neurodegeneration: Translational studies in the CART eraR01MH112391 · NIMH · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI BERMAN, JOAN WEINBERGER, MORGELLO, SUSAN · 2017 to 2021
$3.7M
Understanding Alzheimer's Disease in the Context of the Aging BrainRF1AG054108 · NIA · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI CUERVO, ANA MARIA · 2016 to 2016
$2.1M
NCI NIH HHS P30 CA013330NIAID NIH HHS P30 AI124414NIAID NIH HHS T32 AI070117NIA NIH HHS P01 AG031782NIA NIH HHS P30 AG038072NIA NIH HHS R37 AG021904NIA NIH HHS RF1 AG054108NIDA NIH HHS R01 DA044584NIDA NIH HHS R01 DA048609NIMH NIH HHS R01 MH112391NINDS NIH HHS U54 NS100717
6 · The paper itself

Abstract

A significant number of people living with HIV (PLWH) develop HIV-associated neurocognitive disorders (HAND) despite highly effective antiretroviral therapy (ART). Dysregulated macroautophagy (autophagy) is implicated in HAND pathogenesis. The viral protein Nef, expressed even with suppressive ART, and certain antiretrovirals affect autophagy in non-CNS cells. Astrocytes, vital for CNS microenvironment homeostasis and neuronal health, require autophagy for their own homeostasis. We hypothesized that extracellular Nef and/or ART impact astrocyte autophagy, thus contributing to HAND. We studied in-bulk and selective autophagic flux in primary human astrocytes treated with extracellular Nef and/or a combination of tenofovir+emtricitabine+raltegravir (ART) using Western blotting, a tandem fluorescent LC3 reporter, and transmission electron microscopy/morphometry. We show that after 24 h treatment, Nef and ART decrease autophagosomes through different mechanisms. While Nef accelerates autophagosome degradation without inducing autophagosome formation, ART inhibits autophagosome formation. Combination Nef+ART further depletes autophagosomes by inducing both abnormalities. Additionally, extracellular Nef and/or ART inhibit lysosomal degradation of p62, indicating Nef and/or ART affect in-bulk and selective autophagy differently. Dysregulation of both autophagic processes is maintained after 7 days of Nef and/or ART treatment. Persistent autophagy dysregulation due to chronic Nef and/or ART exposure may ultimately result in astrocyte and neuronal dysfunction, contributing to HAND.

Indexed as

Anti-Retroviral AgentsAstrocytesAutophagyHIV InfectionsHumansnef Gene Products, Human Immunodeficiency VirusNeurocognitive DisordersAnti-Retroviral Agentsnef Gene Products, Human Immunodeficiency Virusantiretroviral therapyastrocytesautophagyHIV-associated neurocognitive disordersLC3Nefp62/SQTM1

Identifiers

PMID32526847
PMCPMC7349791
OpenAlexW3034184959

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.