       Document 0611
 DOCN  M9610611
 TI    An autocrine loop of HIV type-1 Tat protein responsible for the improved
       survival/proliferation capacity of permanently Tat-transfected cells and
       required for optimal HIV-1 LTR transactivating activity.
 DT    9601
 AU    Zauli G; La Placa M; Vignoli M; Re MC; Gibellini D; Furlini G; Milani D;
       Marchisio M; Mazzoni M; Capitani S; Institute of Human Anatomy,
       University of Ferrara, Italy.
 SO    J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Nov 1;10(3):306-16.
       Unique Identifier : AIDSLINE MED/96027798
 AB    Human immunodeficiency virus type 1 (HIV-1) transactivating Tat protein
       is pivotal to virus replication. Tat's potential effects on HIV-1
       pathogenesis, however, go well beyond its role in the virus's life
       cycle. Current data indicate that biologically active Tat is released
       from HIV-1-infected cells and readily endocytosed and targeted to the
       nucleus of nearby, or perhaps distant, cells, where it may exert a
       series of pleiotropic effects. This paracrine action has been
       extensively investigated, and depending on the amounts of exogenously
       added Tat, its effects may extend from the suppression of
       immunocompetent cells to transactivation of heterologous genes to the
       promotion of growth of Kaposi's sarcoma spindle cells. We have already
       observed that various cell lines, either permanently transfected with an
       expressive HIV-1 tat gene construct or cultured in the presence of
       exogenously added Tat protein, are protected from programmed cell death
       after serum withdrawal or other apoptotic stimuli. The present article
       shows that various types (lymphoblastoid, epithelial, neuronal) of
       permanently tat-transfected cell lines actively release fully bioactive
       Tat protein. The addition of anti-Tat antibody to the culture medium
       completely abolishes their increased survival/proliferation capacity in
       serum-free culture. In these conditions, therefore, the enhanced
       survival/proliferation potential of permanently tat-transfected cells
       seems entirely dependent on a Tat-protein autocrine loop. The finding
       that anti-Tat antibody, added to culture medium, exerts a negative
       influence on the expression of a Tat-responsive HIV-1 long terminal
       repeat chloramphenicol-acetyltransferase construct, transiently
       transfected into permanently tat-transfected cells, suggests that the
       Tat autocrine loop may also be required for optimal HIV-1 long terminal
       repeat transactivation.
 DE    Animal  Antibodies/PHARMACOLOGY  Cell Division/PHYSIOLOGY  Cell Line
       Cell Survival/PHYSIOLOGY  Cells, Cultured  Chloramphenicol
       Acetyltransferase/ANALYSIS  Culture Media, Conditioned  Culture Media,
       Serum-Free  Gene Products, tat/BIOSYNTHESIS/CHEMISTRY/*PHYSIOLOGY
       Genes, tat/*GENETICS  Human  HIV Long Terminal Repeat/*PHYSIOLOGY
       HIV-1/*PHYSIOLOGY  Rats  Receptors, Vitronectin/BIOSYNTHESIS  Support,
       Non-U.S. Gov't  *Trans-Activation (Genetics)  Transfection/*GENETICS
       Tumor Cells, Cultured  Virus Replication  JOURNAL ARTICLE

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

