Evidence map›Paper›PMID 27726055›Full record

ArticleJournal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology2017

HIV-1 Viral Protein R Activates NLRP3 Inflammasome in Microglia: implications for HIV-1 Associated Neuroinflammation.

Manmeet K Mamik, Elizabeth Hui, William G Branton, Brienne A McKenzie, Jesse Chisholm, Eric A Cohen, Christopher Power

Abstract read
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In one paragraph

Article in Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.

0numbers the graph read from it
0cells of the map it votes in
89citing papers in PubMed
6.4field-weighted citation impact, top 3% 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

89 citing papers in PubMed, 153 citations in OpenAlex.

  1. Trial
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  7. Epigenetic mechanisms of HIV and opioid-induced neuropathology: Potential therapies and interventions.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  8. Article
  9. Article
  10. Article
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  12. Targeting inflammasomes as a therapeutic potential for HIV/AIDS.Cellular and molecular life sciences : CMLS · 2025
    Review
  13. Review
  14. Article
  15. Review
  16. Article
  17. Review
  18. Review
  19. Article
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29 more citing papers are in PubMed but not listed here.

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

7 authors at 2 institutions in 1 country.

Manmeet K MamikDepartment of Medicine, University of Alberta, T6G 2S2, Edmonton, AB, Canada.
Elizabeth HuiDepartment of Medicine, University of Alberta, T6G 2S2, Edmonton, AB, Canada.
William G BrantonDepartment of Medicine, University of Alberta, T6G 2S2, Edmonton, AB, Canada.
Brienne A McKenzieDepartment of Medicine, University of Alberta, T6G 2S2, Edmonton, AB, Canada.
Jesse ChisholmDepartment of Medicine, University of Alberta, T6G 2S2, Edmonton, AB, Canada.
Eric A CohenInstitut de recherches cliniques de Montréal (IRCM) and Department of Microbiology, Infectiology and Immunology, Université de Montréal, Montreal, QC, Canada.
Christopher PowerDepartment of Medicine, University of Alberta, T6G 2S2, Edmonton, AB, Canada. chris.power@ualberta.ca.
University of Alberta · CAMontreal Clinical Research Institute · CA

Funding

CIHR
6 · The paper itself

Abstract

Human Immunodeficiency virus (HIV) enters the brain soon after seroconversion and induces chronic neuroinflammation by infecting and activating brain macrophages. Inflammasomes are cytosolic protein complexes that mediate caspase-1 activation and ensuing cleavage and release of IL-1β and -18 by macrophages. Our group recently showed that HIV-1 infection of human microglia induced inflammasome activation in NLRP3-dependent manner. The HIV-1 viral protein R (Vpr) is an accessory protein that is released from HIV-infected cells, although its effects on neuroinflammation are undefined. Infection of human microglia with Vpr-deficient HIV-1 resulted in reduced caspase-1 activation and IL-1β production, compared to cells infected with a Vpr-encoding HIV-1 virus. Vpr was detected at low nanomolar concentrations in cerebrospinal fluid from HIV-infected patients and in supernatants from HIV-infected primary human microglia. Exposure of human macrophages to Vpr caused caspase-1 cleavage and IL-1β release with reduced cell viability, which was dependent on NLRP3 expression. Increased NLRP3, caspase-1, and IL-1β expression was evident in HIV-1 Vpr transgenic mice compared to wild-type littermates, following systemic immune stimulation. Treatment with the caspase-1 inhibitor, VX-765, suppressed NLRP3 expression with reduced IL-1β expression and associated neuroinflammation. Neurobehavioral deficits showed improvement in Vpr transgenic animals treated with VX-765. Thus, Vpr-induced NLRP3 inflammasome activation, which contributed to neuroinflammation and was abrogated by caspase-1 inhibition. This study provides a new therapeutic perspective for HIV-associated neuropsychiatric disease.

Indexed as

AdultAged, 80 and overAnimalsCells, CulturedCell SurvivalFemaleFetusHIV-1HumansInflammasomesInflammationInflammation MediatorsMaleMiceMice, TransgenicMicrogliaInflammasomesInflammation MediatorsNLR Family, Pyrin Domain-Containing 3 ProteinNLRP3 protein, humanvpr Gene Products, Human Immunodeficiency VirusHIV-1InflammasomesInterleukin-1 betaNeuroinflammationNLRP3Viral protein R

Identifiers

PMID27726055
OpenAlexW2528029690

What OpenQuestion holds

Textmetadata
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.