Basic fibroblast growth factor (bFGF) and human immunodeficiency virus type 1 (HIV-1) Tat protein synergize in inducing angiogenic Kaposi's sarcoma-like lesions in mice. Synergy is due to Tat, which enhances endothelial cell growth and type-IV collagenase expression in response to bFGF mimicking extracellular matrix proteins. The bFGF, extracellular Tat and Tat receptors are present in HIV-1-associated KS, which may explain the higher frequency and aggressiveness of this form compared to classical Kaposi's sarcoma where only bFGF is present.

277 transactivator proteins of human retroviruses may mediate both viral and cellular effects. However, the events associated with the release, the uptake, and the biological effects of extracellular Tat are not yet well understood. In this study, we investigated whether during acute infection of T cells by HIV-1, Tat is released at concentrations sufficient to stimulate HIV-1 gene expression in a paracrine fashion and the events associated with the release of biologically active protein by cells transfected with the tat gene. As the Tat-containing supematants from both HIV-1-infected and Tat-transfected cells stimulate maximal AIDS-KS cell growth but only low levels of HIV-1 gene expression, we analyzed the kinetics of dose-response for these activities. This analysis was done by using recombinant purified Tat protein in assays of AIDS-KS cell growth, LTR-directed gene expression, and viral replication. Since the nuclear uptake of Tat is a prerequisite for transactivation, we also determined the concentration of exogenous protein necessary to detect nuclear-localized Tat with AIDS-KS cells. The results from these studies suggest that different pathways mediate the cellular and viral effects of extracellular Tat protein. MATERIALS AND METHODS Cell cultures. The T-cell lines H9 and Jurkat, the epithelial cell line COS-1, and HeLa-CD4+ cells containing a Tatdefective HIV-1 provirus (HLM1 cell line) have all been previously described (14, 44). Primary cell cultures derived from KS lesions of patients with AIDS were established and cultured as previously described (14, 16, 37, 38, 46). HIV-1 infection. H9 or Jurkat cells (106/ml) were infected by a cell-free method (14) with HIV-1 (IIIB isolate), as

Kaposi's sarcoma (KS) is a proliferative disease of vascular origin particularly frequent in HIV-1-infected homosexual men (AIDS-KS) and characterized by proliferating spindleshaped cells, angiogenesis, and inflammatory cell infiltration. Previous work has suggested that KS spindle cells are of endothelial cell origin and that chronic immune activation via the release of inflammatory cytokines may cooperate with basic fibroblast growth factor (bFGF) and the HIV-1 Tat protein in the induction and progression of AIDS-KS. Invest. 1995Invest. .95:1723Invest. -1734

The human immunodeficiency virus (HIV) type 1 Tat protein plays a key role in the life cycle of the virus and in pathogenesis and is highly conserved among HIV subtypes. On the basis of this and of safety, immunogenicity, and efficacy findings in monkeys, Tat is being tested as a vaccine in phase 1 trials. Here, we evaluated the incidence and risk of progression to advanced HIV disease by anti-Tat serostatus in a cohort of 252 HIV-1 seroconverters. The risk of progression was lower in the anti-Tat-positive subjects than in the anti-Tat-negative subjects. Progression was faster in the persistently anti-Tat-negative subjects than in the transiently anti-Tat-positive subjects, and no progression was observed in the persistently anti-Tat-positive subjects.