Human immunodeficiency virus-induced apoptosis of human hepatocytes via CXCR4.
Human immunodeficiency virus (HIV) infection is commonly associated with liver dysfunction. The X4 HIV glycoprotein 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 apoptosis through CXCR4. The apoptotic process is dependent on G(ialpha) protein signaling, yet it is independent of caspase cascade activation. Thus, HIV can directly cause hepatocyte death in humans by signaling through CXCR4, without infecting the cell.
Vlahakis
Stacey R
SR
Division of Infectious Diseases, Mayo Clinic, Rochester, Minnesota 55905, USA. paya@mayo.edu
Villasis-Keever
Angelina
A
Gomez
Timothy S
TS
Bren
Gary D
GD
Paya
Carlos V
CV
D017209:Apoptosis / Q000276:immunology*; D002460:Cell Line; D005434:Flow Cytometry; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015658:HIV Infections / Q000150:complications / Q000276:immunology / Q000473:pathology*; D015497:HIV-1 / Q000276:immunology*; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology* / Q000821:virology*; D006801:Humans; D019718:Receptors, CXCR4 / Q000096:biosynthesis / Q000276:immunology*
D015699:HIV Envelope Protein gp120; D019718:Receptors, CXCR4