Induction of apoptosis by protease-defective particle preparations of human immunodeficiency virus type 1 is specific to a subset of U937-derived subclones.
Several recent reports support the hypothesis that apoptosis occurring in leukocytes of human immunodeficiency virus type 1 (HIV-1)-infected individuals is important in progression to AIDS. Specifically, apoptosis of uninfected bystander cells appears critical in the pathogenesis of disease. Here, we present evidence that protease-defective, gp120-containing HIV-1 (L-2) particle preparations specifically induce apoptosis in cells obtained from a subset of promonocytic U937-derived subclones. The rate of apoptosis induction was inversely correlated with the susceptibility of the U937 subclones to wild-type HIV-1 infection. Three types of apoptosis experiments were performed: DNA content analysis by flow cytometry, apoptotic nuclear degradation by fluorescent microscopy and DNA fragmentation analysis by agarose gel electrophoresis. Kinetic analysis revealed that there was a slower induction of apoptosis by L-2 particle preparations than with tumor necrosis factor (TNF)-alpha or anti-Fas antibody. However, there were no significant differences in the initial binding rates of L-2 particles as well as the binding of TNF-alpha or anti-Fas antibody to the U937 subclones. The basal level of protein kinase C activity was higher in high-type subclones compared with low-type subclones. These results suggest that U937 cells can be divided into at least two subpopulations, one that permits a productive HIV-1 infection but is not subjected to L-2 particle preparation-induced apoptosis, while the other poorly replicates HIV-1 and is subjected to L-2 mediated apoptosis, although at a slower rate than found with TNF-alpha or anti-Fas antibody.
Kameoka
M
M
Section of Serology, Hokkaido University, Sapporo, Japan.
Kimura
T
T
Zhong
Q
Q
Zheng
Y H
YH
Luftig
R B
RB
Ikuta
K
K
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology*; D002999:Clone Cells; D010450:Endopeptidases / Q000172:deficiency*; D015497:HIV-1 / Q000201:enzymology* / Q000472:pathogenicity*; D006801:Humans; D007156:Immunologic Memory; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism; D011493:Protein Kinase C / Q000032:analysis; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D019014:fas Receptor / Q000276:immunology
D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D011493:Protein Kinase C; D010450:Endopeptidases