Evidence map›Paper›PMID 21569583›Full record

ArticleJournal of neuroinflammation2011

Lentiviral vector-mediated stable expression of sTNFR-Fc in human macrophage and neuronal cells as a potential therapy for neuroAIDS.

Shengbo Cao, Chengxiang Wu, Yongbo Yang, Lynn F Sniderhan, Sanjay B Maggirwar, Stephen Dewhurst, Yuanan Lu

Abstract read
In one paragraph

Article in Journal of neuroinflammation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
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

7 citing papers in PubMed.

  1. Trial
  2. Article
  3. Neuropharmacologic Approaches to Restore the Brain's Microenvironment.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2016
    Review
  4. Article
  5. Article
  6. Article
  7. 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

7 authors.

Shengbo CaoDepartment of Public Health Sciences, University of Hawai'i, Honolulu, Hawai'i 96822, USA.
Chengxiang Wu
Yongbo Yang
Lynn F Sniderhan
Sanjay B Maggirwar
Stephen Dewhurst
Yuanan Lu

Funding

Targeted Neuro Protection of HIV-1 Associated Neurologic DiseaseP01MH064570 · NIMH · UNIVERSITY OF ROCHESTER · PI GELBARD, HARRIS A · 2001 to 2014
$19.4M
Platelet-mediated neuroinflammatory response to HIVR01NS066801 · NINDS · UNIVERSITY OF ROCHESTER · PI MAGGIRWAR, SANJAY B. · 2010 to 2020
$3.9M
Inflammatory mechanisms associated with HIV-1 dementiaR01NS054578 · NINDS · UNIVERSITY OF ROCHESTER · PI MAGGIRWAR, SANJAY B. · 2006 to 2016
$3.5M
Training in HIV Replication and PathogenesisT32AI049815 · NIAID · UNIVERSITY OF ROCHESTER · PI WEDEKIND, JOSEPH E · 2001 to 2020
$3.5M
Modeling monocyte and macrophage based gene therapy for neuroAIDSR01MH079717 · NIMH · UNIVERSITY OF HAWAII AT MANOA · PI LU, YUANAN · 2009 to 2013
$1.7M
Development of gene transfer approaches for neuroAIDSS11NS043499 · NINDS · UNIVERSITY OF HAWAII AT MANOA · PI LU, YUANAN · 2002 to 2006
$1.5M
NIAID NIH HHS T32 AI049815NIMH NIH HHS P01 MH064570NIMH NIH HHS R01 MH079717NINDS NIH HHS R01 NS054578NINDS NIH HHS R01 NS066801NINDS NIH HHS S11NS043499
6 · The paper itself

Abstract

backgroundHuman immunodeficiency virus type 1 (HIV-1) infection frequently causes neurologic disease, which is the result of viral replication and activation of macrophages and microglia in the CNS, and subsequent secretion of high levels of neurotoxic products, including tumor necrosis factor-α (TNF-α). We therefore hypothesized that a soluble TNF-α antagonist might have potential utility as a neuroprotective effecter molecule, and conducted proof-of-concept studies to test this hypothesis.

methodsTo develop novel therapeutics for the treatment of neuroAIDS, we constructed and characterized a soluble TNF receptor (sTNFR)-Fc fusion protein with the goal of neutralizing TNF-α, and tested the stability of expression of this gene following delivery by a lentiviral vector.

resultsHigh-titer lentiviral vectors were prepared, allowing efficient transduction of macrophage/glial and neuronal cell lines, as well as primary rat cerebellar neurons. Efficient, stable secretion of sTNFR-Fc was demonstrated in supernatants from transduced cell lines over 20 passages, using both western blot and ELISA. Biological activity of the secreted sTNFR-Fc was confirmed by TNF-specific in vitro protein binding and functional blocking assays. Finally, the secreted protein was shown to protect neuronal cells from TNF-α, HIV-1 Tat-, and gp120-mediated neurotoxicity.

conclusionsThese results demonstrate that lentiviral vector mediated expression of sTNFR-Fc may have potential as a novel therapy for neuroAIDS.

Indexed as

AIDS Dementia ComplexAnimalsCell LineEtanerceptGenetic TherapyGenetic VectorsHumansImmunoglobulin GLentivirusMacrophagesMicrogliaNeuronsRatsRats, Sprague-DawleyReceptors, Tumor Necrosis FactorTumor Necrosis Factor-alphaEtanerceptImmunoglobulin GReceptors, Tumor Necrosis FactorTumor Necrosis Factor-alpha

Identifiers

PMID21569583
PMCPMC3118348

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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.