Document Detail


Binding of human immunodeficiency virus type 1 gp120 to CXCR4 induces mitochondrial transmembrane depolarization and cytochrome c-mediated apoptosis independently of Fas signaling.
MedLine Citation:
PMID:  11462036     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Apoptosis of CD4(+) T lymphocytes, induced by contact between human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (gp120) and its receptors, could contribute to the cell depletion observed in HIV-infected individuals. CXCR4 appears to play an important role in gp120-induced cell death, but the mechanisms involved in this apoptotic process remain poorly understood. To get insight into the signal transduction pathways connecting CXCR4 to apoptosis following gp120 binding, we used different cell lines expressing wild-type CXCR4 and a truncated form of CD4 that binds gp120 but lacks the ability to transduce signals. The present study demonstrates that (i) 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; (ii) this apoptotic process is independent of Fas signaling; and (iii) cooperation with a CD4 signal is not required. In addition, following coculture with cells expressing gp120, a Fas-independent apoptosis involving mitochondria and caspase activation is also observed in primary umbilical cord blood CD4(+) T lymphocytes expressing high levels of CXCR4. Thus, this gp120-mediated apoptotic pathway may contribute to CD4(+) T-cell depletion in AIDS.
Authors:
R Roggero; V Robert-Hebmann; S Harrington; J Roland; L Vergne; S Jaleco; C Devaux; M Biard-Piechaczyk
Related Documents :
15189346 - Transfection of 2,6 and 2,3-sialyltransferase genes and glcnac-transferase genes into h...
9077456 - Specific arrest of spermatogenesis caused by apoptotic cell death in transgenic mice.
12135756 - Keratinocytes enriched for stem cells are protected from anoikis via an integrin signal...
3457976 - Expression of murine gamma fetal antigen in adult hematopoietic tissue and during induc...
22797726 - The blk pathway functions as a tumor suppressor in chronic myeloid leukemia stem cells.
17001346 - Impact on the cytomegalovirus (cmv) viral load by cmv-specific t-cell immunity in recip...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of virology     Volume:  75     ISSN:  0022-538X     ISO Abbreviation:  J. Virol.     Publication Date:  2001 Aug 
Date Detail:
Created Date:  2001-07-19     Completed Date:  2001-08-23     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7637-50     Citation Subset:  IM    
Affiliation:
Laboratoire Infections Rétrovirales et Signalisation Cellulaire CNRS EP 2104, Institut de Biologie, 34060 Montpellier Cedex, France.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Antigens, CD95 / physiology
Apoptosis / physiology*
Cell Line
Cytochrome c Group / physiology
HIV Envelope Protein gp120 / physiology*
HIV Infections / pathology,  virology*
HIV-1 / physiology*
Humans
Membrane Potentials / physiology
Mitochondria / physiology
Receptors, CXCR4 / physiology*
Signal Transduction
Chemical
Reg. No./Substance:
0/Antigens, CD95; 0/Cytochrome c Group; 0/HIV Envelope Protein gp120; 0/Receptors, CXCR4
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  The ribosome binding site of hepatitis C virus mRNA.
Next Document:  Duck hepatitis B virus replication in primary bile duct epithelial cells.