PMID- 9730685
OWN - NLM
STAT- MEDLINE
DCOM- 19981103
LR  - 20180213
IS  - 1021-7401 (Print)
IS  - 1021-7401 (Linking)
VI  - 5
IP  - 3-4
DP  - 1998 May-Aug
TI  - HIV-1 tat molecular diversity and induction of TNF-alpha: implications for 
      HIV-induced neurological disease.
PG  - 184-92
AB  - 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.
FAU - Mayne, M
AU  - Mayne M
AD  - Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada.
FAU - Bratanich, A C
AU  - Bratanich AC
FAU - Chen, P
AU  - Chen P
FAU - Rana, F
AU  - Rana F
FAU - Nath, A
AU  - Nath A
FAU - Power, C
AU  - Power C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Switzerland
TA  - Neuroimmunomodulation
JT  - Neuroimmunomodulation
JID - 9422763
RN  - 0 (Gene Products, tat)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Viral Proteins)
RN  - 0 (tat Gene Products, Human Immunodeficiency Virus)
SB  - IM
MH  - AIDS Dementia Complex/*immunology
MH  - Astrocytoma
MH  - Dose-Response Relationship, Immunologic
MH  - Gene Expression Regulation, Viral
MH  - Gene Products, tat/*genetics/pharmacology
MH  - *Genetic Variation
MH  - HIV-1/*genetics/immunology
MH  - Humans
MH  - Jurkat Cells/virology
MH  - Molecular Sequence Data
MH  - NF-kappa B/genetics/immunology
MH  - RNA, Messenger/analysis
MH  - Sequence Homology, Amino Acid
MH  - Tumor Necrosis Factor-alpha/*genetics/immunology
MH  - U937 Cells/virology
MH  - Viral Proteins/genetics/immunology
MH  - tat Gene Products, Human Immunodeficiency Virus
EDAT- 1998/09/08 02:04
MHDA- 2000/08/16 11:00
CRDT- 1998/09/08 02:04
PHST- 1998/09/08 02:04 [pubmed]
PHST- 2000/08/16 11:00 [medline]
PHST- 1998/09/08 02:04 [entrez]
AID - nim05184 [pii]
AID - 10.1159/000026336 [doi]
PST - ppublish
SO  - Neuroimmunomodulation. 1998 May-Aug;5(3-4):184-92. doi: 10.1159/000026336.