HIV-1 gp120-and gp160-induced apoptosis in cultured endothelial cells is mediated by caspases

The immune dysfunction and cell destruction that occur in the human immunod eficiency virus (HIV)-infected host appear to result from the direct cytopa thic effects of viral infection and the effects of viral proteins on uninfe cted bystander cells, Recently, the alpha-chemokine receptor CXCR4 has been reported to mediate apoptosis in neuronal cells and in CD4(+) and CD8(+) T cells after its binding to HIV-1 envelope proteins. In the current study, it was observed that human umbilical vein endothelial cells (HUVEC) undergo apoptosis after their treatment with the HIV-1 envelope proteins gp120/160 . Anti-CXCR4 monoclonal antibody decreased HIV-1 gp120/160-induced apoptosi s, suggesting that the CXCR4 chemokine receptor mediates the apoptotic effe cts of these HIV envelope glycoproteins, Further studies revealed that casp ases play an important role in this process because the pretreatment of cel ls with a general caspase enzyme inhibitor decreased the extent of HUVEC ap optosis induced by gp120/160, In addition, it was found that caspase-3 was activated on HIV-1 gp120/160 treatment of these cells. It was also observed that gp120/160 treatment slightly increased the expression of the pro apop totic molecule Bar. These results suggest that HIV-1 envelope glycoproteins can disrupt endothelial integrity through the interaction with CXCR4, ther eby facilitating virus transit out of the bloodstream and contributing to t he vascular injury syndromes seen in acquired immunodeficiency syndrome. (B lood. 2000;96:1438-1442) (C) 2000 by The American Society of Hematology.