HIV gp41-induced apoptosis is mediated by caspase-3-dependent mitochondrial depolarization, which is inhibited by HIV protease inhibitor nelfinavir

• DOI: 10.1189/jlb.0805430
• Publication Date: 2005-12-06T01:25:20Z
• Authors: Himanshu Garg; Robert Blumenthal
• Keywords: Nelfinavir; Intrinsic apoptosis

Abstract Apoptotic loss of CD4+ T cells has been proposed as a mechanism cell depletion in human immunodeficiency virus (HIV) infections resulting immunodeficiency. The Env glycoprotein implicated apoptosis uninfected bystander via gp120 binding to CD4/CXC chemokine receptor 4 well the fusion/hemifusion process mediated by gp41. Using an vitro model coculture Env-expressing effectors and targets, we find that fact correlates with gp41-induced hemifusion. Further, apoptotic pathway initiated this interaction involves caspase-3-dependent mitochondrial depolarization reactive oxygen species production. HIV is inhibited protease inhibitor nelfinavir but not other inhibitors or calpain cathepsin. This “kiss death” (hemifusion) signaling independent p38 mitogen-activated protein kinase p53, making it distinct from seen syncytia. We also show virion-induced gp41-dependent. Our findings provide new insights into which gp41 mediates cells.