Human Immunodeficiency Virus-Induced Apoptosis of Human Hepatocytes via CXCR4

Stacey R. Vlahakis, Angelina Villasis-Keever, Timothy S. Gomez, Gary D. Bren, Carlos V. Paya

Research output: Contribution to journalArticle

83 Scopus citations

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, 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.

Original languageEnglish (US)
Pages (from-to)1455-1460
Number of pages6
JournalJournal of Infectious Diseases
Volume188
Issue number10
DOIs
StatePublished - Nov 15 2003

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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