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 immunodeficiency syndrome associated with early qualitative defects in antigen-specific T cell function and with late quantitative defects in CD4+ T lymphocytes. We have observed that peripheral blood mononuclear cells (PBMC) from FIV-infected cats have impaired survival in culture. The mechanism of this in vitro dysfunction and depletion is not known. We have proposed 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 impaired survival in vitro, undergo an active cell death upon culture, which has the morphological and biochemical characteristics of programmed cell death (PCD). Apoptosis occurred in all six asymptomatic FIV-infected cats, and in none of the nine uninfected cats, which were studied. Changes in cell morphology under both light and electron microscopy, and fragmentation of genomic DNA were characteristic for apoptosing cells. Cell death was spontaneous and occurred in the absence of any stimuli, and culture with the T cell mitogen, concanavalin A (Con A), did not 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 endonuclease responsible for the characteristic fragmentation of DNA. Since apoptosis has recently been implicated in AIDS pathogenesis, FIV infection may prove useful to study this aspect of retroviral, in particular HIV, infection.
Bishop
S A
SA
Department of Veterinary Medicine, University of Bristol, UK.
Gruffydd-Jones
T J
TJ
Harbour
D A
DA
Stokes
C R
CR
D000818:Animals; D017209:Apoptosis; D002415:Cats; D016923:Cell Death; D002478:Cells, Cultured; D003470:Culture Media; D004247:DNA / Q000302:isolation & purification; D004249:DNA Damage; D016181:Feline Acquired Immunodeficiency Syndrome / Q000097:blood*; D016089:Immunodeficiency Virus, Feline; D007963:Leukocytes, Mononuclear / Q000648:ultrastructure*; D008213:Lymphocyte Activation; D013047:Specific Pathogen-Free Organisms; D013601:T-Lymphocytes
D003470:Culture Media; D004247:DNA