Evidence map›Paper›PMID 18439272›Full record

ArticleRetrovirology2008

Selective killing of HIV-1-positive macrophages and T cells by the Rev-dependent lentivirus carrying anthrolysin O from Bacillus anthracis.

Jessica Young, Zhongwei Tang, Quan Yu, Dongyang Yu, Yuntao Wu

Open access · goldAbstract read
In one paragraph

Article in Retrovirology, 2008. 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
0.9field-weighted citation impact, top 30% 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, 21 citations in OpenAlex.

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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

5 authors at 2 institutions in 2 countries.

Jessica YoungDepartment of Molecular and Microbiology, George Mason University, Manassas, VA 20110, USA. jyoung4@gmu.edu
Zhongwei Tang
Quan Yu
Dongyang Yu
Yuntao Wu
George Mason University · USShanxi Agricultural University · CN

Funding

Targeting Brain Macrophages by a novel lentiviral vectorR21NS051130 · NINDS · GEORGE MASON UNIVERSITY · PI WU, YUNTAO · 2005 to 2006
$358k
NINDS NIH HHS NS051130NINDS NIH HHS R21 NS051130
6 · The paper itself

Abstract

backgroundThe ability of Human Immunodeficiency Virus (HIV) to persist in the body has proven to be a long-standing challenge to virus eradication. Current antiretroviral therapy cannot selectively destroy infected cells; it only halts active viral replication. With therapeutic cessation or interruption, viral rebound occurs, and invariably, viral loads return to pre-treatment levels. The natural reservoirs harboring replication-competent HIV-1 include CD4 T cells and macrophages. In particular, cells from the macrophage lineage resist HIV-1-mediated killing and support sustained viral production. To develop a complementary strategy to target persistently infected cells, this proof-of-concept study explores an HIV-1 Rev-dependent lentiviral vector carrying a bacterial hemolysin, anthrolysin O (anlO) from Bacillus anthracis, to achieve selective killing of HIV-1- infected cells.

resultsWe demonstrate that in the Rev-dependent lentiviral vector, anlO expression is exclusively dependent on Rev, a unique HIV-1 protein present only in infected cells. Intracellular expression and oligomerization of AnlO result in membrane pore formation and cytolysis. We have further overcome a technical hurdle in producing a Revdependent AnlO lentivirus, through the use of beta-cyclodextrin derivatives to inhibit direct killing of producer cells by AnlO. Using HIV-1-infected macrophages and T cells as a model, we demonstrate that this Rev-dependent AnlO lentivirus diminishes HIV-1- positive cells.

conclusionThe Rev-dependent lentiviral vector has demonstrated its specificity in targeting persistently infected cells. The choice of anlO as the first suicidal gene tested in this vector is based on its cytolytic activity in macrophages and T cells. We conclude that Rev-regulated expression of suicidal genes in HIV-1-positive cells is possible, although future in vivo delivery of this system needs to address numerous safety issues.

Indexed as

Bacillus anthracisBacterial Proteinsbeta-CyclodextrinsCell DeathCells, CulturedDNA, ViralGenetic VectorsGreen Fluorescent ProteinsHIV-1HumansLentivirusMacrophagesMembrane Glycoproteinsrev Gene Products, Human Immunodeficiency VirusT-Lymphocytesanthrolysin O, Bacillus anthracisBacterial Proteinsbeta-CyclodextrinsDNA, ViralGreen Fluorescent ProteinsMembrane Glycoproteinsrev Gene Products, Human Immunodeficiency Virus

Identifiers

PMID18439272
PMCPMC2391154
OpenAlexW1982125287

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.