EVIDENCE FOR STIMULATION OF THE TRANSFORMING GROWTH-FACTOR-BETA-1 PROMOTER BY HIV-1 TAT IN CELLS DERIVED FROM CNS

Infection by human immunodeficiency virus type 1 (HIV-1), the etiologi c agent of the acquired immunodeficiency syndrome (AIDS), is often com plicated with a high incidence of neurologic disorders. It is believed that HIV-1, in addition to infecting both macroglial and microglial c ells, may influence the expression of several strategic genes of uninf ected neighboring or latently infected brain cells. It is suspected th at the viral-encoded transregulatory protein, Tat, facilitates cross-c ommunications between these cells. In support of this concept, earlier studies demonstrated that Tat is released from the infected cells, an d has the capacity to be taken up by the uninfected cells and exert it s biological activity on the responsive gene. Recent studies in severa l laboratories suggest the involvement of Tat in altering the expressi on of a limited number of cellular regulatory factors which, in turn, may mediate the altered physiology of the cells. In this communication , we demonstrate the ability of the HIV-1 Tat protein to increase expr ession of transforming growth factor beta1 (TGF-beta1), a cytokine wit h potent immunosuppressive activity, in human astrocytic glial cells. Implications of the Tat-mediated induction of TGF-beta1 expression and cytokine involvement in the regulation of immune response and central nervous system (CNS) pathology are discussed.