Abstract 201: Transfer of Intracellular HIV-Nef to Endothelium Causes MCP-1 Release and Induction of Apoptosis
With effective antiretroviral therapy (ART), cardiovascular diseases (CVD) are emerging as a major cause of morbidity and death in the aging HIV-infected population. To address whether HIV-Nef, a viral protein produced in infected cells even when virus production is halted by ART, can lead to endothelial activation and dysfunction, we tested Nef protein transfer to and activity in endothelial cells. We demonstrated that Nef protein from either HIV-infected or Nef-transfected T cells rapidly transfers to endothelial cells while inducing nanotube-like conduits connecting T cells to endothelial cells. This transfer to or transfection of endothelial cells resulted in apoptosis, ROS generation and release of monocyte attractant protein-1 (MCP-1). Nef-induced apoptosis is mediated through both NADPH oxidase- and ROS-dependent mechanisms, while MCP-1 production is NF-κB dependent. Importantly, Nef protein can be found in circulating blood cells in patients receiving virally suppressive ART, and in the endothelium of chimeric SIV-infected macaques. Together, these data indicate that inhibition of Nef-associated pathways may be promising new therapeutic targets for reducing the risk for cardiovascular disease in the HIV-infected population.
- © 2013 by American Heart Association, Inc.