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Activation-associated necrosis in human immunodeficiency virus infection

Borthwick, NJ; Wickremasinghe, RG; Lewin, J; Fairbanks, LD; Bofill, M; (1999) Activation-associated necrosis in human immunodeficiency virus infection. J INFECT DIS , 179 (2) 352 - 360.

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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.

Type: Article
Title: Activation-associated necrosis in human immunodeficiency virus infection
Keywords: PROGRAMMED CELL-DEATH, T-CELLS, HIV-1 INFECTION, IN-VITRO, LYMPHOCYTE-ACTIVATION, INDUCED APOPTOSIS, DNA FRAGMENTATION, GENE-EXPRESSION, TNF FAMILY, DE-NOVO
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: http://discovery.ucl.ac.uk/id/eprint/121830
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