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Imaging of HIV-1 Envelope-induced Virological Synapse and Signaling on Synthetic Lipid Bilayers
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Imaging of HIV-1 Envelope-induced Virological Synapse and Signaling on Synthetic Lipid Bilayers

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NF-kappaB activation upon interaction of HIV-1 envelope glycoproteins with cell surface CD4 involves IkappaB kinases

Guillaume Bossis1, Sara Salinas, Christine Cartier

  • 1Laboratoire Infections Rétrovirales et Signalisation Cellulaire, CNRS UMR 5121, Institut de Biologie, 4 Bd Henri IV, 34060, Montpellier, France.

FEBS Letters
|April 18, 2002
PubMed

Insights

Human immunodeficiency virus type-1 (HIV-1) envelope glycoprotein gp120 binding to CD4 receptors activates the NF-kappaB pathway. This involves IkappaB kinases (IKKs) phosphorylating IkappaB-alpha, leading to T cell activation.

Area of Science:

  • Immunology
  • Molecular Biology
  • Virology

Background:

  • Human immunodeficiency virus type-1 (HIV-1) envelope glycoprotein gp120 binding to CD4 receptors initiates T cell activation.
  • Nuclear translocation of the transcription factor NF-kappaB is a key intracellular event following gp120-CD4 interaction.

Purpose of the Study:

  • To investigate the specific signal transduction pathways mediating gp120-induced NF-kappaB activation.
  • To elucidate the role of IkappaB kinases (IKKs) and IkappaB-alpha in this process.

Main Methods:

  • Studied the effect of gp120-CD4 interaction on IkappaB-alpha phosphorylation.
  • Utilized dominant-negative IkappaB-alpha transgenes to assess its role in NF-kappaB activation.
  • Assessed IKKs activity following CD4 engagement with gp120.
  • Employed dominant-negative IKKs in co-transfection experiments.

Main Results:

  • gp120-CD4 interaction stimulates the hyperphosphorylation of the inhibitory protein IkappaB-alpha.
  • Overexpression of a mutated IkappaB-alpha transgene blocked gp120-induced NF-kappaB activation.
  • IKKs activity was selectively enhanced upon CD4 engagement with gp120.
  • Dominant-negative IKKs inhibited gp120-induced NF-kappaB activation, confirming their mediating role.

Conclusions:

  • The IKKs complex plays a critical role in gp120-induced NF-kappaB activation.
  • This pathway is crucial for T cell activation and cell cycle entry following HIV-1 envelope engagement.

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