Mechanisms of apoptosis induction by the HIV-1 envelope

J. L. Perfettini, M. Castedo, T. Roumier, K. Andreau, R. Nardacci, M. Piacentini, G. Kroemer

Research output: Contribution to journalArticle

Abstract

The envelope glycoprotein complex (Env) of human immunodeficiency virus-1 (HIV-1) can induce apoptosis by a cornucopia of distinct mechanisms. A soluble Env derivative, gp120, can kill cells through signals that are transmitted by chemokine receptors such as CXCR4. Cell surface-bound Env (gp120/gp41), as present on the plasma membrane of HIV-1-infected cells, can kill uninfected bystander cells expressing CD4 and CXCR4 (or similar chemokine receptors, depending on the Env variant) by at least three different mechanisms. First, a transient interaction involving the exchange of lipids between the two interacting cells ('the kiss of death') may lead to the selective death of single CN-expressing target cells. Second, fusion of the interacting cells may lead to the formation of syncytia which then succumb to apoptosis in a complex pathway involving the activation of several kinases (cyclin-dependent kinase-1, Cdk1; checkpoint kinase-2, Chk2; mammalian target of rapamycin, mTOR; p38 mitogen-activated protein kinase, p38 MAPK; inhibitor of NF-κB kinase, IKK), as well as the activation of several transcription factors (NF-κB, p53), finally resulting in the activation of the mitochondrial pathway of apoptosis. Third, if the Env-expressing cell is at an early stage of imminent apoptosis, its fusion with a CD4-expressing target cell can precipitate the death of both cells, through a process that may be considered as contagious apoptosis and which does not involve Cdk1, mTOR, p38 nor p53, yet does involve mitochondria. Activation of some of the above- mentioned lethal signal transducers have been detected in patients' tissues, suggesting that HIV-1 may indeed trigger apoptosis through molecules whose implication Env-induced killing has initially been discovered in vitro.

Original languageEnglish
Pages (from-to)916-923
Number of pages8
JournalCell Death and Differentiation
Volume12
Issue numberSUPPL. 1
DOIs
Publication statusPublished - Aug 2005

Keywords

  • AIDS
  • gp120
  • gp41
  • Mitochondria
  • p53
  • Programmed cell death

ASJC Scopus subject areas

  • Cell Biology

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  • Cite this

    Perfettini, J. L., Castedo, M., Roumier, T., Andreau, K., Nardacci, R., Piacentini, M., & Kroemer, G. (2005). Mechanisms of apoptosis induction by the HIV-1 envelope. Cell Death and Differentiation, 12(SUPPL. 1), 916-923. https://doi.org/10.1038/sj.cdd.4401584