Programmed cell death (apoptosis) as a mechanism of cell death in peripheral blood mononuclear cells from cats infected with feline immunodeficiency virus (FIV)

Abstract

SUMMARY FIV is a lentivirus infection of cats which induces an immunodeficiency syndrome associated with curly qualitative defects in antigen‐specific T cell function and with late quantitative detects 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 eats, 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.

Clinical Aspects of Feline Retroviruses: A Review

“…In addition, an increase in the proportion of CD8 + cells also contributes to the inversion [104,108,110], in particular a population referred to as “CD8 + alpha-hi, beta-low cells” [111,112,113], a subset of CD8 + cells that may contribute to suppression of viremia in FIV-infected cats. Causes of CD4 + cell loss include decreased production secondary to bone marrow or thymic infection, lysis of infected cells induced by FIV itself (cytopathic effects), destruction of virus-infected cells by the immune system, or death by apoptosis (cell death that follows receipt of a membrane signal initiating a series of programmed intracellular events) [114,115,116,117,118,119,120,121,122,123,124,125,126]. The degree of apoptosis correlates inversely with the CD4 + numbers and the CD4/CD8 ratio [127].…”

Clinical aspects of feline immunodeficiency and feline leukemia virus infection

“…Causes of CD4 + cell loss include decreased production secondary to bone marrow or thymic infection, lysis of infected cells induced by FIV itself (cytopathic effects), destruction of virus-infected cells by the immune system, or death by apoptosis (cell death that follows receipt of a membrane signal initiating a series of programmed intracellular events) (Bishop et al, 1993;Ohno et al, 1993Ohno et al, , 1994Johnson et al, 1996;Guiot et al, 1997a,b;Mizuno et al, 1997;Mortola et al, 1998a,b;Piedimonte et al, 1999;Mizuno et al, 2001Mizuno et al, , 2003bTompkins et al, 2002). The degree of apoptosis correlates inversely with CD4 + numbers and the CD4/CD8 ratio (Holznagel et al, 1998).…”

The effects of Avemar treatment on feline immunodeficiency virus infected cell cultures

“…Earlier studies have shown that FIV‐M2‐infected MBM cells lysed without syncytia formation (Matteucci et al., 1995 ), and we have previously shown that acute FIV‐M2 infection of MBM cells elicits programmed cell death (Tarcsai et al., 2021 ). FIV is known to induce apoptosis of acutely infected, IL‐2‐dependent T‐lymphoid MYA‐1 cells (Ohno et al., 1994 ) and peripheral blood lymphocytes of cats (Bishop et al., 1993 ).…”