TY - JOUR
T1 - Mechanisms of apoptosis induction by the HIV-1 envelope
AU - Perfettini, J. L.
AU - Castedo, M.
AU - Roumier, T.
AU - Andreau, K.
AU - Nardacci, R.
AU - Piacentini, M.
AU - Kroemer, G.
PY - 2005/1/1
Y1 - 2005/1/1
N2 - 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 CD4-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-jB kinase, IKK), as well as the activation of several transcription factors (NF-jB, 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 in Envinduced killing has initially been discovered in vitro.
AB - 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 CD4-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-jB kinase, IKK), as well as the activation of several transcription factors (NF-jB, 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 in Envinduced killing has initially been discovered in vitro.
KW - Aids
KW - Gp120
KW - Gp41
KW - Mitochondria
KW - P53
KW - Programmed cell death
UR - http://www.scopus.com/inward/record.url?scp=22744435902&partnerID=8YFLogxK
U2 - 10.1038/sj.cdd.4401584
DO - 10.1038/sj.cdd.4401584
M3 - Review article
C2 - 15719026
AN - SCOPUS:22744435902
SN - 1350-9047
VL - 12
SP - 916
EP - 923
JO - Cell Death and Differentiation
JF - Cell Death and Differentiation
ER -