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

doi:10.1086/379738

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

Infectious Diseases

Research output: Contribution to journal › Article › peer-review

89 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_iα, 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 language	English (US)
Pages (from-to)	1455-1460
Number of pages	6
Journal	Journal of Infectious Diseases
Volume	188
Issue number	10
DOIs	https://doi.org/10.1086/379738
State	Published - Nov 15 2003

ASJC Scopus subject areas

General Medicine

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10.1086/379738

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title = "Human Immunodeficiency Virus-Induced Apoptosis of Human Hepatocytes via CXCR4",

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 Giα, 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.",

author = "Vlahakis, {Stacey R.} and Angelina Villasis-Keever and Gomez, {Timothy S.} and Bren, {Gary D.} and Paya, {Carlos V.}",

note = "Funding Information: Received 12 March 2003; accepted 25 June 2003; electronically published 18 November 2003. Financial support: National Institutes of Health grant #RO1 AI40384. Reprints or correspondence: Dr. Carlos V. Paya, Div. of Infectious Diseases, Mayo Clinic, 200 First St. SW, Guggenheim 501, Rochester, MN 55905 (paya@mayo.edu).",

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T1 - Human Immunodeficiency Virus-Induced Apoptosis of Human Hepatocytes via CXCR4

AU - Vlahakis, Stacey R.

AU - Villasis-Keever, Angelina

AU - Gomez, Timothy S.

AU - Bren, Gary D.

AU - Paya, Carlos V.

N1 - Funding Information: Received 12 March 2003; accepted 25 June 2003; electronically published 18 November 2003. Financial support: National Institutes of Health grant #RO1 AI40384. Reprints or correspondence: Dr. Carlos V. Paya, Div. of Infectious Diseases, Mayo Clinic, 200 First St. SW, Guggenheim 501, Rochester, MN 55905 (paya@mayo.edu).

PY - 2003/11/15

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N2 - 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 Giα, 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.

AB - 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 Giα, 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.

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Human Immunodeficiency Virus-Induced Apoptosis of Human Hepatocytes via CXCR4

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