HIV-1 infection of human CD4+ T cells in vitro. Differential induction of apoptosis in these cells.
The H9 and CEM CD4+ T cell lines were infected with HIV-1 (NY5/LAV-1 isolate) and monitored for losses in cell viability, syncytium formation, and internucleosomal DNA cleavage (a marker for apoptosis). H9 cells were found to undergo cell death via apoptosis as a result of HIVNY5 infection, but this effect was not apparent in CEM cell cultures. The differential effects of HIV-1NY5 in terms of its apoptosis-inducing properties correlated with the relative abilities of H9 and CEM cells in supporting replication of this HIV-1 isolate, since infected CEM cell cultures produced 10-fold lower levels of HIV-1 p24 protein, and very few of these cells stained positive for cell-associated p24 by comparison with H9 cell cultures infected at the same multiplicity of infection. Furthermore, a different HIV-1 isolate (RF), which replicated equally efficiently in both H9 and CEM cells, produced similar levels of apoptosis in these cultures. HIV-1NY5 was also found to be capable of inducing apoptosis in purified peripheral blood CD4+ T cells as well as inhibiting anti-CD3-driven proliferation of these cells. In contrast, incubation of purified CD8+ T cells with HIV-1NY5 under similar conditions produced no cytopathic effects. Substantial levels of apoptosis were also recorded in HIV-1NY5-infected PHA blasts cell cultures. Soluble rHIV-1IIIB type CHO-derived gp120 was found to mimic the effects of HIV in terms of inhibition of anti-CD3/TCR mAb-induced proliferation of T cells, but apoptosis was not detected in gp120-treated T cell cultures whether cross-linked or used in conjunction with anti-CD3 mAb or not. We conclude therefore that both HIV-1NY5 and HIV-1RF isolates have the capacity to directly trigger apoptotic cell death in CD4+ T cells and that this appears to be at least partly associated with the efficiency of virus replication in these cells.
Martin
S J
SJ
Department of Immunology, University College London Medical School, UK.
Matear
P M
PM
Vyakarnam
A
A
D017209:Apoptosis / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000382:microbiology* / Q000502:physiology; D016827:CD8 Antigens / Q000097:blood; D002460:Cell Line; D004249:DNA Damage; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D016176:T-Lymphocyte Subsets / Q000382:microbiology / Q000502:physiology
D016827:CD8 Antigens; D016655:HIV Core Protein p24