Both necrosis and apoptosis contribute to HIV-1-induced killing of CD4 cells

Douglas R. Plymale, Derek S. Ng Tang, Alla M. Comardelle, César D. Fermin, Dorothy E. Lewis, Robert F. Garry

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

Background: Data currently available on HIV-1-induced cytopathology is unclear regarding the mechanism of cell killing. Objective: To clarify the extent to which apoptosis or necrosis is involved in HIV-1-induced cell death in view of conflicting exiting data. Methods: T lymphoblastoid cells or peripheral blood mononuclear cells were infected by various strains of HIV-1 and the number of apoptotic or necrotic cells were quantified at various times after infection using video-image analysis techniques; the results were compared with the amount of fragmented DNA using a quantitative method. Measurement of mitochondrial transmembrane potential (ΔΨ(m)) and intracellular calcium concentrations [Ca2+](i) was performed with fluorescent probes and fluorescence concentration analysis (FCA). Results: Although lymphoblastoid and monocytoid cells acutely infected by HIV-1 had increased levels of fragmented DNA, a marker of apoptotic cell death, few (< 12%) had condensed chromatin and fragmented nuclei, the morphological features of apoptosis. The predominant alterations in acutely infected cells were distended endoplasmic reticulum and abnormal mitochondria; these ultrastructural changes are consistent with necrosis, although some infected cells simultaneously displayed features of both necrosis and apoptosis. Viability of cells persistently infected by HIV-1 was only minimally reduced from that of uninfected cells. This reduction was accounted for by an increased propensity of the persistently infected cells to die by apoptosis. Alterations in [Ca2+](i) and ΔΨ(m) occurred in both acutely and persistently infected cells. Conclusion: Both necrosis and apoptosis contribute to HIV-1-induced killing of CD4 cells.

Original languageEnglish (US)
Pages (from-to)1827-1839
Number of pages13
JournalAIDS
Volume13
Issue number14
DOIs
StatePublished - 1999

Keywords

  • Apoptosis
  • CD4
  • Calcium
  • Cell death
  • HIV-1
  • Mitochondria
  • Necrosis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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