Evidence map›Paper›PMID 21645334›Full record

ArticleRetrovirology2011

Interactions between human immunodeficiency virus (HIV)-1 Vpr expression and innate immunity influence neurovirulence.

Hong Na, Shaona Acharjee, Gareth Jones, Pornpun Vivithanaporn, Farshid Noorbakhsh, Nicola McFarlane, Ferdinand Maingat, Klaus Ballanyi, Carlos A Pardo, Eric A Cohen and 1 more

Open access · goldAbstract read
In one paragraph

Article in Retrovirology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
1.1field-weighted citation impact, top 25% 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

24 citing papers in PubMed, 36 citations in OpenAlex.

  1. Review
  2. Observational
  3. Article
  4. Review
  5. Article
  6. Review
  7. Emerging Role of Nef in the Development of HIV Associated Neurological Disorders.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2021
    Review
  8. Review
  9. Article
  10. HIV-1 Viral Protein R Activates NLRP3 Inflammasome in Microglia: implications for HIV-1 Associated Neuroinflammation.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2017
    Article
  11. Review
  12. Time-Dependent, HIV-Tat-Induced Perturbation of Human NeuronsFrontiers in molecular neuroscience · 2017
    Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Differential type 1 interferon-regulated gene expression in the brain during AIDS: interactions with viral diversity and neurovirulence.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2013
    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

11 authors at 4 institutions in 3 countries.

Hong NaDepartment of Medicine University of Alberta, Edmonton, AB, T6G 2S2, Canada. chris.power@ualberta.ca.
Shaona Acharjee
Gareth Jones
Pornpun Vivithanaporn
Farshid Noorbakhsh
Nicola McFarlane
Ferdinand Maingat
Klaus Ballanyi
Carlos A Pardo
Eric A Cohen
Christopher Power
University of Alberta · CAJohns Hopkins Medicine · USUniversité de Montréal · CAUniversity of Calgary · CA

Funding

HIV infection and drugs of abuse in neuroglial functionK08DA016160 · NIDA · JOHNS HOPKINS UNIVERSITY · PI PARDO-VILLAMIZAR, CARLOS A · 2003 to 2007
$870k
Canadian Institutes of Health ResearchNIDA NIH HHS K08 DA 16160
6 · The paper itself

Abstract

backgroundViral diversity and abundance are defining properties of human immunodeficiency virus (HIV)-1's biology and pathogenicity. Despite the increasing availability of antiretroviral therapy, HIV-associated dementia (HAD) continues to be a devastating consequence of HIV-1 infection of the brain although the underlying disease mechanisms remain uncertain. Herein, molecular diversity within the HIV-1 non-structural gene, Vpr, was examined in RNA sequences derived from brain and blood of HIV/AIDS patients with or without HIV-associated dementia (HAD) together with the ensuing pathobiological effects.

resultsCloned brain- and blood-derived full length vpr alleles revealed that amino acid residue 77 within the brain-derived alleles distinguished HAD (77Q) from non-demented (ND) HIV/AIDS patients (77R) (p < 0.05) although vpr transcripts were more frequently detected in HAD brains (p < 0.05). Full length HIV-1 clones encoding the 77R-ND residue induced higher IFN-α, MX1 and BST-2 transcript levels in human glia relative to the 77Q-HAD encoding virus (p < 0.05) but both viruses exhibited similar levels of gene expression and replication. Myeloid cells transfected with 77Q-(pVpr77Q-HAD), 77R (pVpr77R-ND) or Vpr null (pVpr(-))-containing vectors showed that the pVpr77R-ND vector induced higher levels of immune gene expression (p < 0.05) and increased neurotoxicity (p < 0.05). Vpr peptides (amino acids 70-96) containing the 77Q-HAD or 77R-ND motifs induced similar levels of cytosolic calcium activation when exposed to human neurons. Human glia exposed to the 77R-ND peptide activated higher transcript levels of IFN-α, MX1, PRKRA and BST-2 relative to 77Q-HAD peptide (p < 0.05). The Vpr 77R-ND peptide was also more neurotoxic in a concentration-dependent manner when exposed to human neurons (p < 0.05). Stereotaxic implantation of full length Vpr, 77Q-HAD or 77R-ND peptides into the basal ganglia of mice revealed that full length Vpr and the 77R-ND peptide caused greater neurobehavioral deficits and neuronal injury compared with 77Q-HAD peptide-implanted animals (p < 0.05).

conclusionsThese observations underscored the potent neuropathogenic properties of Vpr but also indicated viral diversity modulates innate neuroimmunity and neurodegeneration.

Indexed as

Polymorphism, GeneticViral TropismAmino Acid SequenceAnimalsAntigens, CDBloodBone Marrow Stromal Antigen 2BrainGene Expression ProfilingGPI-Linked ProteinsGTP-Binding ProteinsHIV-1HumansImmunity, InnateInterferon-alphaMaleAntigens, CDBone Marrow Stromal Antigen 2BST2 protein, humanGPI-Linked ProteinsGTP-Binding ProteinsInterferon-alphaMx1 protein, mouseMyxovirus Resistance ProteinsRNA, Viralvpr Gene Products, Human Immunodeficiency Virus

Identifiers

PMID21645334
PMCPMC3123635
OpenAlexW2159358871

What OpenQuestion holds

Textmetadata
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.