title: Activation-associated necrosis in human immunodeficiency virus infection.
abstract: 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.
authors.affiliation: Department of Clinical Immunology, Royal Free and University College Medical School, Royal Free Hospital, London NW3 2PF, United Kingdom.
authors.forename: N J
authors.initials: NJ
authors.lastname: Borthwick
authors.forename: R G
authors.initials: RG
authors.lastname: Wickremasinghe
authors.forename: J
authors.initials: J
authors.lastname: Lewin
authors.forename: L D
authors.initials: LD
authors.lastname: Fairbanks
authors.forename: M
authors.initials: M
authors.lastname: Bofill
mesh_terms: 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
chemical_list: D017252:CD3 Complex; D018956:CD5 Antigens; D016207:Cytokines; D009711:Nucleotides