Induced Apoptosis of Human

Human immunodeficiency virus (HIV) infection is com-monly associated with liver dysfunction. The X4 HIV gly-coprotein 120 envelope (env) induces apoptosis in T cells and neurons via the HIV coreceptor CXCR4. Therefore, we investigated whether hepatocyte death could result from the HIV env signaling through CXCR4 on the hepatocyte. We demonstrated that hepatocytes in humans express CXCR4 on the cell surface. Furthermore, we established that the X4 HIV env and the entire HIV virion signal hepatocyte ap-optosis through CXCR4. The apoptotic process is dependent on Gia protein signaling, yet it is independent of caspase cascade activation. Thus, HIV can directly cause hepatocyte death in humans by signaling through CXCR4, without in-fecting the cell. Liver dysfunction causes significant morbidity among huma