Apoptotic effects in primary human umbilical vein endothelial cell cultures caused by exposure to virion-associated and cell membrane-associated HIV-1 gp120

During the course of HIV-I infection, free virus, infected cells, and free HIV-I proteins circulate within the host, exposing the host endothelium to these viral factors. We have previously presented evidence showing that sol uble HIV-I gp120 protein interacts with chemokine receptors on primary huma n endothelium and (through those interactions) induces apoptosis as well as other intracellular effects. The current study examines the effect of expo sure of vascular endothelium to gp120 IIIb expressed on the surface of Jurk at cells and in the context of viral particles. Apoptosis was observed in h uman umbilical vein endothelial cell (HUVEC) cultures exposed to gp 160-tra nsfected Jurkat cells as well as to virion particles with gp 120 on their s urface. Additional experiments show that this apoptotic effect was caused b y gp120 protein acting through chemokine receptors on the HUVEC surface, pr imarily the CXCR4 receptor. At higher concentrations of gp120, this lymphot rophic variant, which has been shown to interact predominantly with CXCR4, seems to interact with and induce apoptosis through the CCR5 receptor. Fina lly, this apoptotic effect in HUVEC cultures occurs at low levels of the in ducing agent, gp120, on cell membranes or on virion particles. These result s demonstrate that HIV-I gp120 is capable of interacting with and killing v ascular endothelial cells in multiple in vivo contexts.