Human immunodeficiency virus type 2 (HIV-2)-infected baboons (Papio cynocephalus) provide a valuable animal model for the study of acquired immunodeficiency syndrome (AIDS) pathogenesis since many features of disease progression resemble HIV-1-infection of humans. In some HIV-2-infected baboons that are clinically healthy, a CD8+ cell antiviral response, that is partly mediated by a soluble factor, controls viral replication in vitro. In the present study, we demonstrate that CD8+ cells derived from HIV-2-infected baboon peripheral blood, lymph nodes, adenoids and tonsils had antiviral activity in co-cultures of CD8+ and CD4+ cells that inversely correlates with viral load. A soluble factor was found to be active against the chemokine-resistant, syncytium-inducing HIV-1(SF2) and HIV-1(SF33) isolates and was relatively heat stable at 100 degrees C for 10 min. Moreover, inhibition of the transcription from the long terminal repeat of HIV-1 was observed in 1G5 cells after activation with phorbol 12-myristate 13-acetate. Therefore, the soluble suppressing activity of CD8+ cells in HIV-2-infected baboons may be analogous to the CD8+ cell antiviral factor described in human HIV-infected asymptomatic people. (C) 1999 Elsevier Science B.V. All rights reserved.