HIV-1 Tat molecular diversity and induction of TNF-α

Implications for HIV-induced neurological disease

Michael Mayne, Ana Christina Bratanich, Peiqin Chen, Farazana Rana, Avindra Nath, Christopher Power

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)184-192
Number of pages9
JournalNeuroImmunoModulation
Volume5
Issue number3-4
DOIs
StatePublished - 1998
Externally publishedYes

Fingerprint

HIV-1
Tumor Necrosis Factor-alpha
HIV
Brain
Macrophages
Spleen
Clone Cells
Human Immunodeficiency Virus Proteins
Type C Phospholipases
Sequence Homology
Cyclic AMP-Dependent Protein Kinases
Neuroglia
Astrocytes
Protein-Tyrosine Kinases
Blood Cells
Acquired Immunodeficiency Syndrome
Genome
Cell Line
Messenger RNA
Infection

Keywords

  • Astrocytes
  • Brain
  • HIV-1
  • Macrophages
  • Molecular diversity
  • NF-κB
  • Tat
  • TNF-α

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)
  • Immunology

Cite this

HIV-1 Tat molecular diversity and induction of TNF-α : Implications for HIV-induced neurological disease. / Mayne, Michael; Bratanich, Ana Christina; Chen, Peiqin; Rana, Farazana; Nath, Avindra; Power, Christopher.

In: NeuroImmunoModulation, Vol. 5, No. 3-4, 1998, p. 184-192.

Research output: Contribution to journalArticle

Mayne, Michael ; Bratanich, Ana Christina ; Chen, Peiqin ; Rana, Farazana ; Nath, Avindra ; Power, Christopher. / HIV-1 Tat molecular diversity and induction of TNF-α : Implications for HIV-induced neurological disease. In: NeuroImmunoModulation. 1998 ; Vol. 5, No. 3-4. pp. 184-192.
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