Document 0074
 DOCN  M9490074
 TI    Human immunodeficiency virus type 1 Tat activity in human neuronal
       cells: uptake and trans-activation.
 DT    9411
 AU    Kolson DL; Collman R; Hrin R; Balliet JW; Laughlin M; McGann KA; Debouck
       C; Gonzalez-Scarano F; Department of Neurology, University of
       Pennsylvania Medical; Center, Philadelphia 19104.
 SO    J Gen Virol. 1994 Aug;75 ( Pt 8):1927-34. Unique Identifier : AIDSLINE
       MED/94321982
 AB    Neurological dysfunction in AIDS occurs in the absence of productive
       infection of neurons, and may involve modulation of neuronal cell
       function by viral or cellular products released from surrounding
       infected cells. The human immunodeficiency virus type 1 (HIV-1)
       trans-activator protein Tat may be one such factor, as it can act as a
       neurotoxin, induces marked morphological changes in neurons and
       astrocytes in primary embryonic rodent brain cultures, and is released
       by certain HIV-1-infected cells. In addition, Tat can alter expression
       of cellular genes in several non-neuronal cell types. To explore the
       possibility that Tat may also mediate neuronal dysfunction in AIDS
       through non-lethal effects on neurons, we determined the
       trans-activating ability of Tat in human neuronal cells. We generated
       human neuronal cell lines stably expressing several HIV-1 tat genes, and
       also tested human neuronal cells exposed to extracellular recombinant
       Tat protein. Both endogenously expressed Tat as well as exogenous
       recombinant Tat protein up-regulated HIV-1 long terminal region
       (LTR)-driven gene expression by several hundred-fold. Only brief
       exposure to recombinant Tat was necessary and no toxic effects were seen
       at levels sufficient for trans-activation. Furthermore, Tat
       significantly enhanced virus expression in neuronal cells transfected
       with molecular clones of HIV-1. These results show that Tat is
       trans-activationally active in human neuronal cells, and can be taken up
       from the extracellular compartment by these cells in a biologically
       active form. Neurons represent an important potential target for
       Tat-mediated cellular dysfunction.
 DE    *Gene Expression Regulation, Viral  Gene Products,
       tat/*GENETICS/*METABOLISM  Human  HIV Antigens/METABOLISM  HIV Long
       Terminal Repeat/GENETICS  HIV-1/GROWTH &
       DEVELOPMENT/*GENETICS/IMMUNOLOGY  Neurons/*METABOLISM
       Proviruses/GENETICS  Support, Non-U.S. Gov't  Support, U.S. Gov't,
       P.H.S.  *Trans-Activation (Genetics)  Transfection  Tumor Cells,
       Cultured  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).