J Infect Dis. 2003 Oct 15;188(8):1192-204. Epub 2003 Sep 30.

Hepatitis C and human immunodeficiency virus envelope proteins cooperatively induce hepatocytic apoptosis via an innocent bystander mechanism.

Munshi N, Balasubramanian A, Koziel M, Ganju RK, Groopman JE.

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Divisions of Experimental Medicine and Infectious Diseases, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, Boston, Massachusetts 02115, USA.

Abstract

We hypothesized that hepatocytes exposed to hepatitis C virus (HCV) and human immunodeficiency virus (HIV) might be injured via an "innocent bystander" mechanism due to cell-surface binding of viral proteins. To assess this, we studied the effects of HCV envelope protein E2 and T-tropic HIV envelope glycoprotein gp120 on hepatocytes and saw potent apoptosis. Either viral protein alone did not induce this effect. HCV E2 and M-tropic HIV gp120 also induced significant apoptosis. Blocking the CXCR4 receptor led to a reduction in apoptosis. HCV E2 and HIV gp120 acted collaboratively to trigger a specific set of downstream signaling events, including up-regulation of the Fas ligand and dephosphorylation of the anti-apoptotic molecule AKT. These results suggest that hepatic injury may occur in HCV/HIV coinfection through the induction of novel downstream signaling pathways and provide a rationale for therapeutic interventions that interfere with specific receptors and signaling molecules.

PMID:: 14551890; [PubMed - indexed for MEDLINE]

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