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Imaging of HIV-1 Envelope-induced Virological Synapse and Signaling on Synthetic Lipid Bilayers
Published on: March 8, 2012
Caveolin-1 modulates HIV-1 envelope-induced bystander apoptosis through gp41
Xiao Mei Wang1, Peter E Nadeau, Yung-Tsun Lo
1Department of Infectious Disease and Pathology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611, USA.
Journal of Virology
|April 16, 2010
Summary
Caveolin-1 (Cav-1) limits Human Immunodeficiency Virus (HIV) envelope-induced bystander apoptosis by inhibiting membrane fusion and caspase activation. This interaction offers a potential therapeutic strategy against HIV pathogenesis.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Human immunodeficiency virus (HIV) envelope (Env) causes CD4(+) T cell loss via bystander apoptosis.
- This apoptosis is gp41-dependent and linked to membrane hemifusion.
- Caveolin-1 (Cav-1), a lipid raft protein, interacts with gp41, but its role is unclear.
Purpose of the Study:
- To investigate the role of cellular Cav-1 in modulating HIV Env-induced bystander apoptosis.
- To elucidate the pathological or physiological significance of the Cav-1 and gp41 interaction.
Main Methods:
- Examined Cav-1 and HIV gp41 interaction within lipid rafts in SupT1 cells and primary CD4(+) T lymphocytes.
- Assessed the impact of Cav-1 on Env-induced membrane hemifusion and caspase-3 activation.
- Evaluated the effect of a Cav-1 scaffold domain peptide on apoptosis.
Main Results:
- Cav-1 significantly suppressed Env-induced membrane hemifusion and caspase-3 activation.
- Cav-1 augmented Hsp70 upregulation in response to Env.
- A Cav-1 scaffold domain peptide markedly inhibited bystander apoptosis and related signaling pathways.
Conclusions:
- Cav-1 plays a crucial role in limiting HIV Env-induced bystander apoptosis.
- The Cav-1/gp41 interaction within lipid rafts is a key mechanism.
- Cav-1 represents a potential therapeutic target for mitigating HIV pathogenesis.
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