J Infect Dis. 2003 Nov 15;188(10):1455-60. Epub 2003 Nov 18.

Human immunodeficiency virus-induced apoptosis of human hepatocytes via CXCR4.

Vlahakis SR, Villasis-Keever A, Gomez TS, Bren GD, Paya CV.

Source

Division of Infectious Diseases, Mayo Clinic, Rochester, Minnesota 55905, USA. paya@mayo.edu

Abstract

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.

PMID:: 14624370; [PubMed - indexed for MEDLINE]

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R01 AI40384/AI/NIAID NIH HHS/United States

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