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Table of Contents
Vol. 5, No. 3-4, 1998
Issue release date: May – August
Section title: Paper
Neuroimmunomodulation 1998;5:184–192
(DOI:10.1159/000026336)

HIV-1 Tat Molecular Diversity and Induction of TNF-α: Implications for HIV-Induced Neurological Disease

Mayne M.a · Bratanich A.C.a · Chen P.a · Rana F.b · Nath A.c · Power C.a
a Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada; b Department of Pathology, University of Nairobi, Kenya; c Departments of Neurology, Microbiology and Immunology, University of Kentucky, Lexington, Ky., USA

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Article / Publication Details

First-Page Preview
Abstract of Paper

Published online: September 04, 1998
Issue release date: May – August

Number of Print Pages: 9
Number of Figures: 3
Number of Tables: 2

ISSN: 1021-7401 (Print)
eISSN: 1423-0216 (Online)

For additional information: http://www.karger.com/NIM

Abstract

Activation and infection by HIV-1 of glial cells and infiltrating macrophages are cardinal features of AIDS-related neurological disease. Tumor necrosis factor-α (TNF-α) is released by these cell types, and increased TNF-α 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-α. We review our data showing the induction of TNF-α by Tat in primary human fetal astrocytes, human peripheral blood mononuclear cells, macrophages, and astrocytic and macrophage cell lines. TNF-α induction was NF-κB 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-α production and thus may play a key role in the pathogenesis of HIV-related neurological disease.


Article / Publication Details

First-Page Preview
Abstract of Paper

Published online: September 04, 1998
Issue release date: May – August

Number of Print Pages: 9
Number of Figures: 3
Number of Tables: 2

ISSN: 1021-7401 (Print)
eISSN: 1423-0216 (Online)

For additional information: http://www.karger.com/NIM


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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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