Effect of extracellular human immunodeficiency virus type 1 glycoprotein 120 on primary human vascular endothelial cell cultures

During the course of an HIV-1 infection, free infectious and noninfectious virus particles, and free HIV-1 proteins, circulate within the host, exposi ng the host endothelium to these viral factors, even if the endothelium is not infected. This suggests that extracellular HIV-1 proteins could influen ce endothelial cell function, leading to pathogenesis, In light of this, we have used primary cultured human vascular endothelial cells (HUVECs) to sc reen for effects of the HIV-1 protein gp120 on endothelial cell. function. The results of this study show that short exposure of HUVEC cultures to thi s protein causes significant levels of cytotoxicity, Further, using several different assays, we have shown that this cytotoxic effect on HUVECs appea rs to be due to induction of an apoptotic program. The biphasic nature of g p120 titration curves suggests that multiple cellular factors are mediating these gp120-induced effects. Competition studies appear to confirm this by showing that the apoptotic effect is mediated through two cell surface rec eptors on HUVECs, CCR5 and CXCR4, Alternatively, competition studies examin ing CD4 receptors suggests that CD4 played no role in gp120-induced effects on HUVECs.