Linked Life Data

9730685

Source:http://linkedlifedata.com/resource/pubmed/id/9730685

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3-4
pubmed:dateCreated
1998-11-3
pubmed:abstractText
Activation and infection by HIV-1 of glial cells and infiltrating macrophages are cardinal features of AIDS-related neurological disease. Tumor necrosis factor-alpha (TNF-alpha) is released by these cell types, and increased TNF-alpha mRNA and protein levels are associated with the development and severity of HIV-induced neurological disease. HIV-1 proteins have been implicated in HIV neuropathogenesis including Tat which has been shown to be a potent inducer of TNF-alpha. We review our data showing the induction of TNF-alpha by Tat in primary human fetal astrocytes, human peripheral blood mononuclear cells, macrophages, and astrocytic and macrophage cell lines. TNF-alpha induction was NF-kappaB dependent and was eliminated by inhibiting protein kinase A, phospholipase C and protein tyrosine kinase activity. In addition, we examined the molecular diversity of the tat genome in the brains of HIV-infected patients from different HIV-1 clades. Comparison of matched brain- and spleen-derived tat sequences indicated that homology among brain-derived clones was greater than that between the brain- and spleen-derived clones. The brain-derived tat sequences were markedly heterogeneous in regions which influence viral replication and intracellular transport. Future studies using Tat, encoded by different sequences, will be necessary to determine the functional significance of tat molecular diversity. Nonetheless, these studies suggest that Tat is an important inducer of TNF-alpha production and thus may play a key role in the pathogenesis of HIV-related neurological disease.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1021-7401
pubmed:author
pubmed:issnType
Print
pubmed:volume
5
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
184-92
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:9730685-AIDS Dementia Complex, pubmed-meshheading:9730685-Astrocytoma, pubmed-meshheading:9730685-Dose-Response Relationship, Immunologic, pubmed-meshheading:9730685-Gene Expression Regulation, Viral, pubmed-meshheading:9730685-Gene Products, tat, pubmed-meshheading:9730685-Genetic Variation, pubmed-meshheading:9730685-HIV-1, pubmed-meshheading:9730685-Humans, pubmed-meshheading:9730685-Jurkat Cells, pubmed-meshheading:9730685-Molecular Sequence Data, pubmed-meshheading:9730685-NF-kappa B, pubmed-meshheading:9730685-RNA, Messenger, pubmed-meshheading:9730685-Sequence Homology, Amino Acid, pubmed-meshheading:9730685-Tumor Necrosis Factor-alpha, pubmed-meshheading:9730685-U937 Cells, pubmed-meshheading:9730685-Viral Proteins, pubmed-meshheading:9730685-tat Gene Products, Human Immunodeficiency Virus
pubmed:articleTitle
HIV-1 tat molecular diversity and induction of TNF-alpha: implications for HIV-induced neurological disease.
pubmed:affiliation
Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't