Linked Life Data

10680847

Source:http://linkedlifedata.com/resource/pubmed/id/10680847

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2000-3-16
pubmed:abstractText
Studies have demonstrated that human immunodeficiency virus type 1 (HIV-1) infection of central nervous system (CNS)-based cells in vivo results in a series of devastating clinical conditions collectively termed acquired immune deficiency syndrome (AIDS) dementia complex (ADC). Gene therapy for these neurovirological disorders necessitates utilization of a vector system that can mediate in vivo delivery and long-term expression of an antiretroviral transgene in nondividing/postmitotic CNS cellular elements. The present studies focus on the transfer of an anti-HIV-1 gene to primary isolated CNS microvascular endothelial cells (MVECs) and neuronal-based cells, for its effects in protecting these cells from HIV-1 infection. By using an HIV-1-based vector system, it was possible to efficiently transduce and maintain expression of a marker transgene, beta-galactosidase (beta-Gal), in human CNS MVECs, human fetal astrocytes, plus immature and mature (differentiated) NT2 cells. Significant transduction of the marker gene, beta-Gal, in CNS-based cells prompted the utilization of this system with an anti-HIV-1 gene therapeutic construct, RevM10, a trans-dominant negative mutant Rev protein. Initially, it was not possible to generate any HIV-1 vector particles with the RevM10 gene in the transducing construct, because of inhibitory effects on the HIV-1 vector by this gene product. However, the vector could be partially rescued by adding an additional construct that supplied wild-type rev, in trans, during a multiple construct transfection in the packaging 293T cells. Thus, it was possible to significantly improve the titer of RevM10-expressing viral particles generated from these cells. Moreover, this RevM10 vector transduced the neuronal precursor cell line NT2, retinoic acid-differentiated human neurons (hNT) from the precursor cells, and primary isolated human brain MVECs with high efficiency. RevM10 generated from the HIV-1-based vector system potently inhibited replication of diverse HIV-1 strains in human CNS MVECs and neuronal cells. The data generated from these studies represent an initial approach for future development of anti-HIV-1 gene therapy in the CNS.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1043-0342
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
347-59
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10680847-AIDS Dementia Complex, pubmed-meshheading:10680847-Brain, pubmed-meshheading:10680847-Cell Differentiation, pubmed-meshheading:10680847-Dose-Response Relationship, Drug, pubmed-meshheading:10680847-Endothelium, Vascular, pubmed-meshheading:10680847-Fluorescent Antibody Technique, pubmed-meshheading:10680847-Gene Therapy, pubmed-meshheading:10680847-Genes, rev, pubmed-meshheading:10680847-HIV-1, pubmed-meshheading:10680847-Humans, pubmed-meshheading:10680847-Lentivirus, pubmed-meshheading:10680847-Microcirculation, pubmed-meshheading:10680847-Models, Genetic, pubmed-meshheading:10680847-Neurons, pubmed-meshheading:10680847-Open Reading Frames, pubmed-meshheading:10680847-Time Factors, pubmed-meshheading:10680847-Tretinoin, pubmed-meshheading:10680847-Tumor Cells, Cultured, pubmed-meshheading:10680847-Virus Assembly
pubmed:year
2000
pubmed:articleTitle
Anti-human immunodeficiency virus type 1 gene therapy in human central nervous system-based cells: an initial approach against a potential viral reservoir.
pubmed:affiliation
Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.