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A Critical role for anti‐apoptotic c‐IAP2 gene in LPS and TNF‐a‐induced resistance to HIV‐Vpr mediated apoptosis in human monocytic cell
Author(s) -
Mishra Sasmita,
Mishra Jyoti Prasad,
Kumar Ashok
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a622
Subject(s) - apoptosis , tumor necrosis factor alpha , innate immune system , microbiology and biotechnology , biology , monocyte , cell culture , immune system , immunology , biochemistry , genetics
Monocytic cells which play a central role in both innate and acquired immunity are productively infected by HIV as are CD4 + activated T cells, however, unlike CD4+ T cells, monocytic cells survive HIV replication without major signs of HIV‐induced cytopathic effects. Vpr, one of the accessory proteins of HIV causes apoptosis in various cell types including lymphocytes, and monocytes. It is believed that one of the reasons by which monocytic cells escape HIV‐Vpr‐induced cytopathic effects is the capacity of HIV to decrease its sensitivity to apoptosis most probably by TNF‐α the cytokine known to be produced in abundance in HIV infection. However, the mechanism responsible for the resistance developed by the monocytes to HIV‐Vpr induced apoptosis is not known. In this study, we used C terminal Vpr peptide which is essential to induce apoptosis and demonstrated for the first time that LPS and TNF‐α induced resistance to HIV‐Vpr mediated apoptosis by upregulating c‐IAP2 through the activation of calmodulin‐dependent protein kinase‐II (CaMKII). In contrast, Vpr52‐96 peptide if treated prior to LPS/TNF‐α stimulation abrogated LPS/TNF‐αmediated protective effects against Vpr52‐96‐induced apoptosis. Furthermore, Vpr52‐96 peptide inhibited LPS/TNF‐αmediated protective effects by inhibiting LPS/TNF‐αinduced calcium influx, activation of calmodulin and CaMKII, and NFκB‐mediated c‐IAP2 induction.