Mitochondrial Apoptosis Induced by the HIV‐1 Envelope

  title={Mitochondrial Apoptosis Induced by the HIV‐1 Envelope},
  author={Maria Castedo and Jean-Luc Perfettini and Karine Andr{\'e}au and Thomas Roumier and Mauro Piacentini and Guido Kroemer},
  journal={Annals of the New York Academy of Sciences},
Abstract: The envelope glycoprotein complex (Env), encoded by the human immunodeficiency virus (HIV‐1), kills uninfected cells expressing CD4 and/or the chemokine receptor CXCR4 or CCR5, via at least three independent mechanisms. First, the soluble Env product gp120 can induce the apoptotic cell death of lymphocytes, neurons, and myocardiocytes, via interaction with surface receptors. Second, Env present on the surface of HIV‐1 infected cells can transiently interact with cells expressing CD4… 

Genetic Signatures of HIV-1 Envelope-mediated Bystander Apoptosis

Residues Arg-476 and Asn-425 are associated with differences in HIV-1 Env-mediated bystander apoptosis induction, a phenomenon that correlates inversely with putative N-linked glycosylation sites and positively with virion infectivity.

Mitochondria Influence Fas Expression in GP120-Induced Apoptosis of Neuronal Cells

The results indicate that mitochondrial-death proteins like caspases may influence the upregulation of the death receptor Fas, and the inhibition of caspase prevents gp120-induced apoptosis.

Viral Control of Mitochondrial Apoptosis

The current knowledge on the viral modulation of mitochondrial apoptosis is summarized, by focusing in particular on the mechanisms by which viral proteins control the host cell death apparatus.

Site-specific Mutations in HIV-1 gp41 Reveal a Correlation between HIV-1-mediated Bystander Apoptosis and Fusion/Hemifusion*

Evidence is provided that gp41-mediated hemifusion is both required and sufficient for induction of apoptosis in bystander cells and may help to explain the mechanism of HIV-1 Env-induced T cell depletion.

HIV-1 Infection Is Blocked at an Early Stage in Cells Devoid of Mitochondrial DNA

Analysis of the early steps of virus infection by real-time PCR quantification of stage-specific HIV-1 DNA products in the infected ρ0 and parental cell line have allowed us to conclude that HIV-0 cells are blocked at the steps that occur after reverse transcription and prior to nuclear import.

Soluble HIV-1 gp120 enhances HIV-1 replication in non-dividing CD4+ T cells, mediated via cell signaling and Tat cofactor overexpression

Results show that soluble gp120 contributes to HIV-1 replication and dissemination, via the activation of multiple cell signaling pathways and the induction of Tat-cofactor expression, underscoring its potential as a therapeutic target in HIV- 1-mediated pathogenesis.

Signal transducer and activator of transcription factor 1 mediates apoptosis induced by hepatitis C virus and HIV envelope proteins in hepatocytes.

These studies indicate that the HCV/HIV envelope proteins cooperatively induce hepatocytic apoptosis by activating a novel downstream STAT1 signaling pathway.

Implication of p38 mitogen-activated protein kinase isoforms (alpha, beta, gamma and delta) in CD4+ T-cell infection with human immunodeficiency virus type I.

Results suggest that, in SupT1-based cell lines, p38alpha, p 38gamma and p38delta, but not p38beta, are implicated in both HIV-1 induced replication and apoptosis in infected and uninfected bystander cells.

A Novel Role of Proline Oxidase in HIV-1 Envelope Glycoprotein-induced Neuronal Autophagy*

The first report that demonstrates the functional role of proline oxidase in HIV-1 gp120-mediated neuronal autophagy and a role of POX as a stress response metabolic regulator is demonstrated for the first time.

The role of dynamin in HIV type 1 Env-mediated cell-cell fusion.

It is demonstrated that dynasore, a dynamin inhibitor, suppressed HIV-1 Env-mediated cell-cell fusion and suggested that dynamin 2 might play a role in HIV-2 envelope glycoproteins' role in cell- cell fusion.



Mitochondrial Control of Cell Death Induced by HIV‐1‐Encoded Proteins

The data suggest the possibility that viruses employ multiple strategies to regulate host cell apoptosis by targeting mitochondria, and the structural motifs of the Vpr protein involved in MMP are conserved among most pathogenic HIV‐1 isolates.

Apoptosis Control in Syncytia Induced by the HIV Type 1–Envelope Glycoprotein Complex

The results establish that the following molecular sequence governs apoptosis of Env-induced syncytia: Bax-mediated/Bcl-2–inhibited MMP → AIF release → Cyt-c release → caspase activation → nuclear apoptosis.

Binding of Human Immunodeficiency Virus Type 1 gp120 to CXCR4 Induces Mitochondrial Transmembrane Depolarization and Cytochromec-Mediated Apoptosis Independently of Fas Signaling

The present study demonstrates that the interaction of cell-associated gp120 with CXCR4-expressing target cells triggers a rapid dissipation of the mitochondrial transmembrane potential resulting in the cytosolic release of cytochrome c from the mitochondria to cytosol, concurrent with activation of caspase-9 and -3.

Apoptosis and karyogamy in syncytia induced by the HIV-1-envelope glycoprotein complex

In a model culture system of syncytium-dependent cell death, HeLa cells stably transfected with a lymphotropic HIV-1 Env gene (HeLa Env) were fused by co-culture with CD4/CXCR4-expressing He La cells (Hela CD4), indicating that apoptosis induced by exogenous stimuli obeys other principles than spontaneoussyncytial apoptosis.

HIV induces lymphocyte apoptosis by a p53‐initiated, mitochondrial‐mediated mechanism

  • D. GeniniD. Sheeter L. Leoni
  • Biology, Chemistry
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2001
The results suggest that HIV activates the p53 pathway, leading to cytochrome c and AIF release with ensuing caspase activation, and that HIV kills infected cells directly or indirectly.

The implication of the chemokine receptor CXCR4 in HIV-1 envelope protein-induced apoptosis is independent of the G protein-mediated signalling.

The results suggest that CXCR4 is involved in HIV-1-induced apoptosis; however, this role does not appear to involve G-protein-mediated CX CR4 signalling.

Human immunodeficiency virus 1 envelope-initiated G2-phase programmed cell death.

Aberrancies in cell cycle regulatory proteins initiated by cell-cell contact between T cells expressing HIV-1 envelope glycoproteins and other T cellsExpressing CD4 receptors are described.

Productive HIV-1 Infection of Primary CD4+ T Cells Induces Mitochondrial Membrane Permeabilization Leading to a Caspase-independent Cell Death*

A major role of the mitochondria is suggested in the process of CD4 T cell death induced by HIV, in which targeting of Bax to the mitochondia may be involved.

The HIV-1 Viral Protein R Induces Apoptosis via a Direct Effect on the Mitochondrial Permeability Transition Pore

Coincubation of purified organelles revealed that nuclear apoptosis is only induced by Vpr when mitochondria are present yet can be abolished by PTPC inhibitors, suggesting that Vpr induces apoptosis via a direct effect on the mitochondrial PTPC.

HIV-1 envelope induces activation of caspase-3 and cleavage of focal adhesion kinase in primary human CD4(+) T cells.

  • C. CicalaJ. Arthos A. Fauci
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2000
It is demonstrated that in primary T lymphocytes, recombinant HIV-1 envelope proteins induce the activation of caspase-3 and caspases, which belong to a family of cysteine proteases that, upon activation, promote programmed cell death.