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Preparation and Use of HIV-1 Infected Primary CD4+ T-Cells as Target Cells in Natural Killer Cell Cytotoxic Assays
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Preparation and Use of HIV-1 Infected Primary CD4+ T-Cells as Target Cells in Natural Killer Cell Cytotoxic Assays

Published on: March 14, 2011

Concentration-dependent differential induction of necrosis or apoptosis by HIV-1 lytic peptide 1

D R Plymale1, A M Comardelle, C D Fermi

  • 1Interdisciplinary Graduate Program in Molecular and Cellular Biology, Tulane University, New Orleans, LA 70112, USA.

Peptides
|December 28, 1999
PubMed

Insights

Human immunodeficiency virus type 1 (HIV-1) may kill CD4+ T-cells through cytotoxic viral proteins. Lentivirus lytic peptide type 1 (LLP-1) induces necrosis at high concentrations and apoptosis at low concentrations, suggesting concentration-dependent cell death mechanisms.

Area of Science:

  • Virology
  • Immunology
  • Cell Biology

Background:

  • The depletion of CD4+ T-lymphocytes by human immunodeficiency virus type 1 (HIV-1) is a hallmark of AIDS.
  • The precise mechanisms driving CD4+ T-cell loss, particularly the role of cytotoxic viral proteins, remain incompletely understood.
  • The HIV-1 transmembrane glycoprotein is implicated in viral entry and potentially in direct cellular toxicity.

Purpose of the Study:

  • To investigate the cytotoxic effects of synthetic peptides derived from the HIV-1 transmembrane glycoprotein on CD4+ T-lymphoblastoid cells.
  • To determine if these peptides induce necrosis or apoptosis and if the mechanism is concentration-dependent.
  • To explore the potential role of viral protein concentration in dictating the mode of HIV-1-mediated cell death.

Main Methods:

  • Synthesis of lentivirus lytic peptide type 1 (LLP-1) corresponding to the carboxyl terminus of the HIV-1 transmembrane glycoprotein.
  • Treatment of CD4+ T-lymphoblastoid cells with varying concentrations of LLP-1 (e.g., 20 nM, 100 nM and above).
  • Microscopic and biochemical analysis to assess cellular integrity, mitochondrial function, and identify characteristics of necrosis and apoptosis.

Main Results:

  • LLP-1 induced significant cytopathology at concentrations of 100 nM and higher.
  • At high concentrations, LLP-1 disrupted mitochondrial integrity and induced features of necrosis in CD4+ T-lymphoblastoid cells.
  • At a lower concentration of 20 nM, LLP-1 potently induced apoptosis in these cells.

Conclusions:

  • The mechanism of HIV-1-mediated CD4+ T-cell death may be concentration-dependent, with cytotoxic viral proteins like LLP-1 capable of inducing either necrosis or apoptosis.
  • Tissue concentration of the HIV-1 transmembrane glycoprotein could influence whether infected cells undergo necrotic or apoptotic cell death.
  • These findings provide insights into the complex pathogenesis of HIV-1 infection and T-cell depletion.

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