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Published on: July 1, 2013
Mitochondrial apoptosis induced by the HIV-1 envelope
Maria Castedo1, Jean-Luc Perfettini, Karine Andreau
1Centre National de la Recherche Scientifique, UMR 8125, Institut Gustave Roussy, F-94805 Villejuif, France.
Annals of the New York Academy of Sciences
|March 23, 2004
Summary
The human immunodeficiency virus (HIV-1) envelope glycoprotein complex (Env) induces cell death through multiple mechanisms, including apoptosis. Env triggers mitochondrial membrane permeabilization, releasing factors that contribute to cell death in HIV-1 infection.
Area of Science:
- Virology
- Cell Biology
- Immunology
Background:
- The human immunodeficiency virus (HIV-1) envelope glycoprotein complex (Env) plays a critical role in viral entry and pathogenesis.
- Uninfected cells expressing CD4 and chemokine receptors (CXCR4 or CCR5) are susceptible to Env-mediated killing.
- Understanding the mechanisms of Env-induced cell death is crucial for developing therapeutic strategies against HIV-1.
Purpose of the Study:
- To elucidate the mechanisms by which the HIV-1 Env complex induces apoptosis in uninfected cells.
- To investigate the role of mitochondrial pathways in Env-mediated cell death.
- To explore the implications of these findings for HIV-1 pathophysiology.
Main Methods:
- Analysis of Env-induced apoptosis in various cell types (lymphocytes, neurons, myocardiocytes).
- Investigation of Env-receptor interactions leading to hemifusion and syncytium formation.
- Assessment of mitochondrial membrane permeabilization (MMP) markers, including mitochondrial transmembrane potential loss, and release of cytochrome c and AIF.
- Evaluation of signaling pathways involved in Env-triggered MMP, such as cytosolic Ca(2+) levels, reactive oxygen species, and p53 activation.
Main Results:
- HIV-1 Env induces apoptosis via at least three mechanisms: soluble gp120-mediated apoptosis, hemifusion-induced cell death, and syncytium formation followed by apoptosis.
- Early signs of Env-induced apoptosis include mitochondrial membrane permeabilization (MMP), characterized by loss of mitochondrial transmembrane potential and release of cytochrome c and AIF.
- Env-triggered MMP may involve elevated cytosolic Ca(2+), reactive oxygen species, and p53-mediated transcriptional activation of pro-apoptotic proteins like Bax.
Conclusions:
- HIV-1 Env utilizes multiple pathways to induce apoptosis in susceptible cells, highlighting its potent cytopathic effects.
- Mitochondrial dysfunction is a key event in Env-induced apoptosis, involving the release of critical apoptotic factors.
- These findings provide insights into the pathophysiology of HIV-1 infection and suggest potential targets for therapeutic intervention.
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