Volume 272, Number 36, Issue of September 5, 1997 pp. 22385-22388
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

COMMUNICATION:
The Tat Protein of HIV-1 Induces Tumor Necrosis Factor- Production
IMPLICATIONS FOR HIV-1-ASSOCIATED NEUROLOGICAL DISEASES

(Received for publication, May 29, 1997, and in revised form, July 3, 1997)

Peiqin Chen , Michael Mayne , Christopher Power ^¶ and Avindra Nath ^¶

From the Department of  Medical Microbiology and Section of Neurology, ^¶ Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada R3E 0W3

Human immunodeficiency virus (HIV) infection may cause a dementing illness. HIV-mediated dementia is clinically and pathologically correlated with the infiltration of activated macrophages and elevated levels of tumor necrosis factor (TNF)-, both of which occur in an environment of small numbers of infected cells. We examined the possibility that HIV protein Tat, which is released extracellularly from infected cells, may induce the production of TNF-. Tat induced TNF- mRNA and protein production dose-dependently, primarily in macrophages but also in astrocytic cells. The TNF- induction was NF-B-dependent and could be eliminated by inhibiting protein kinase A or protein tyrosine kinase activity. In addition, Tat-induced TNF- release was also linked to phospholipase C activation. However, Tat effects were independent of protein kinase C. These observations suggest that Tat may provide an important link between HIV and macrophage/glial cell activation and suggest new therapeutic approaches for HIV dementia.

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