Premium
HIV gp41‐induced apoptosis is mediated by caspase‐3‐dependent mitochondrial depolarization, which is inhibited by HIV protease inhibitor nelfinavir
Author(s) -
Garg Himanshu,
Blumenthal Robert
Publication year - 2006
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0805430
Subject(s) - gp41 , biology , apoptosis , microbiology and biotechnology , nelfinavir , caspase , programmed cell death , protease , intrinsic apoptosis , virology , biochemistry , immunology , human immunodeficiency virus (hiv) , antibody , antiretroviral therapy , viral load , epitope , enzyme
Apoptotic loss of CD4+ T cells has been proposed as a mechanism of T cell depletion in human immunodeficiency virus (HIV) infections resulting in immunodeficiency. The Env glycoprotein has been implicated in apoptosis of uninfected bystander cells via gp120 binding to CD4/CXC chemokine receptor 4 as well as the fusion/hemifusion process mediated by gp41. Using an in vitro model of coculture of Env‐expressing cells as effectors and CD4+ T cells as targets, we find that apoptosis mediated by Env glycoprotein in bystander cells in fact correlates with gp41‐induced hemifusion. Further, the apoptotic pathway initiated by this interaction involves caspase‐3‐dependent mitochondrial depolarization and reactive oxygen species production. HIV gp41‐induced mitochondrial depolarization is inhibited by protease inhibitor nelfinavir but not by other HIV protease inhibitors or inhibitors of calpain and cathepsin. This “kiss of death” (hemifusion) signaling pathway is independent of p38 mitogen‐activated protein kinase and p53, making it distinct from the apoptosis seen in syncytia. We also show that virion‐induced apoptosis is gp41‐dependent. Our findings provide new insights into the mechanism via which HIV gp41 mediates apoptosis in bystander cells.