PROGRAMMED CELL-DEATH (APOPTOSIS) AS A MECHANISM OF CELL-DEATH IN PERIPHERAL-BLOOD MONONUCLEAR-CELLS FROM CATS INFECTED WITH FELINE IMMUNODEFICIENCY VIRUS (FIV)

FIV is a lentivirus infection of cats which induces an immunodeficienc y syndrome associated wit early qualitative defects in antigen-specifi c T cell function and with late quantitative defects in CD4+ T lymphoc ytes. We have observed that peripheral blood mononuclear cells (PBMC) from FIV-infected cats have impaired survival in culture. The mechanis m of this in vitro dysfunction and depletion is not known. We have pro posed that inappropriate induction of programmed cell death (apoptosis ) could account for these in vitro defects. Here, we report that PBMC from FIV-infected cats, with impaired T cell blastogenesis and impaire d survival in vitro, undergo an active cell death upon culture, which has the morphological and biochemical characteristics of programmed ce ll death (PCD). Apoptosis occurred in all six asymptomatic FIV-infecte d cats, and in none of the nine uninfected cats, which were studied. C hanges in cell morphology under both light and electron microscopy, an d fragmentation of genomic DNA were characteristic for apoptosing cell s. Cell death was spontaneous and occurred in the absence of any stimu li, and culture with the T cell mitogen, concanavalin A (Con A), did n ot significantly enhance cell death. Activation-induced cell death was inhibited, in a dose-dependent manner, by addition to the incubation medium of zinc, which has been shown to inhibit the action of endonucl ease responsible for the characteristic fragmentation of DNA. Since ap optosis has recently been implicated in AIDS pathogenesis, FIV infecti on may prove useful to study this aspect of retroviral, in particular HIV, infection.