title: TRAIL dependent fratricidal killing of gp120 primed hepatocytes by HCV core expressing hepatocytes.
abstract: The mechanism by which HIV and HCV cooperatively accelerate hepatocyte damage is not clearly understood; however, each virus affects the TRAIL: TRAIL-receptor system. We, therefore, questioned whether the independent effects of HCV and HIV combine to synergistically result in TRAIL dependent hepatocyte killing. We describe that Huh7 hepatocytes treated with HIV gp120 results in both increase TRAIL-R2 expression and an acquired sensitivity to TRAIL mediated killing. Moreover HCV infection and HCV core expression alone in Huh7 cells upregulates TRAIL. Co-incubation of HIV gp120 primed hepatocytes with HCV core expressing hepatocytes results in the selective death of the HIV gp120 primed hepatocytes that is selectively blocked by TRAIL-R2-Fc fusion protein. Liver biopsies from HIV mono-infected patients have increased TRAIL-R2; biopsies from HCV infected patients have increased TRAIL, while co-infected liver biopsies have increased PARP cleavage within hepatocytes indicating enhanced apoptosis. These findings suggest a pathogenic model to understand why HIV/HCV co-infection accelerates liver injury.
authors: Division of Infectious Diseases, Mayo Clinic, Rochester, Minnesota, United States of America.
authors: Stacey A
authors: SA
authors: Rizza
authors: Kishore B
authors: KB
authors: Challagundla
authors: Sekar
authors: S
authors: Natesampillai
authors: Gary D
authors: GD
authors: Bren
authors: Jaromir
authors: J
authors: Sykora
authors: Henning
authors: H
authors: Walczak
authors: Andrew D
authors: AD
authors: Badley
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D019898:Autocrine Communication / Q000187:drug effects; D002460:Cell Line; D015870:Gene Expression; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology*; D016174:Hepacivirus / Q000235:genetics* / Q000502:physiology; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism* / Q000821:virology; D006801:Humans; D019899:Paracrine Communication / Q000187:drug effects; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D014758:Viral Core Proteins / Q000235:genetics*
chemical_list: D015699:HIV Envelope Protein gp120; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; D014758:Viral Core Proteins; C514793:gp120 protein, Human immunodeficiency virus 1