Activation-associated necrosis in human immunodeficiency virus infection.
Mitogenic stimulation of lymphocytes from persons infected with human immunodeficiency virus (HIV) resulted in massive cell death. In addition to early apoptosis, a second wave of cell death occurred 48-72 h after stimulation. At that time, the cells were enlarged, leaked content, and had plasma membrane damage-all indicative of necrosis. Furthermore, DNA fragmentation as determined by TUNEL assay was virtually absent. This activation-associated necrosis could not be prevented by interfering with CD95/CD95-ligand interactions or by blocking caspase activity and was unaffected by neutralizing antibodies to tumor necrosis factor-alpha or interferon-gamma. Necrosis was also induced by activation of normal lymphocytes in the presence of ribavirin, which inhibits the de novo pathway of nucleotide synthesis. Lymphocytes from HIV-infected persons are defective in their ability to synthesize nucleotides via this pathway, indicating one possible mechanism for the activation-associated necrosis seen in HIV infection.
Borthwick
N J
NJ
Department of Clinical Immunology, Royal Free and University College Medical School, Royal Free Hospital, London NW3 2PF, United Kingdom.
Wickremasinghe
R G
RG
Lewin
J
J
Fairbanks
L D
LD
Bofill
M
M
D000328:Adult; D017209:Apoptosis; D017252:CD3 Complex / Q000032:analysis / Q000276:immunology; D018956:CD5 Antigens / Q000032:analysis / Q000276:immunology; D002452:Cell Count; D016207:Cytokines / Q000276:immunology / Q000494:pharmacology; D015658:HIV Infections / Q000276:immunology / Q000473:pathology*; D006801:Humans; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D009711:Nucleotides / Q000096:biosynthesis
D017252:CD3 Complex; D018956:CD5 Antigens; D016207:Cytokines; D009711:Nucleotides