TRAIL Dependent Fratricidal Killing of gp120 Primed Hepatocytes by HCV Core Expressing Hepatocytes

Stacey Rizza, Kishore B. Challagundla, Sekar Natesampillai, Gary D. Bren, Jaromir Sykora, Henning Walczak, Andrew David Badley

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere27171
JournalPLoS One
Volume6
Issue number11
DOIs
StatePublished - 2011

Fingerprint

hepatocytes
Hepatocytes
HIV Envelope Protein gp120
Biopsy
HIV
Liver
biopsy
liver
TNF-Related Apoptosis-Inducing Ligand Receptors
Coinfection
mixed infection
Viruses
Up-Regulation
Fusion reactions
apoptosis
Apoptosis
death
viruses
receptors
Wounds and Injuries

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

TRAIL Dependent Fratricidal Killing of gp120 Primed Hepatocytes by HCV Core Expressing Hepatocytes. / Rizza, Stacey; Challagundla, Kishore B.; Natesampillai, Sekar; Bren, Gary D.; Sykora, Jaromir; Walczak, Henning; Badley, Andrew David.

In: PLoS One, Vol. 6, No. 11, e27171, 2011.

Research output: Contribution to journalArticle

Rizza, Stacey ; Challagundla, Kishore B. ; Natesampillai, Sekar ; Bren, Gary D. ; Sykora, Jaromir ; Walczak, Henning ; Badley, Andrew David. / TRAIL Dependent Fratricidal Killing of gp120 Primed Hepatocytes by HCV Core Expressing Hepatocytes. In: PLoS One. 2011 ; Vol. 6, No. 11.
@article{ffde0b831b734f678938e5af41cea142,
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.",
author = "Stacey Rizza and Challagundla, {Kishore B.} and Sekar Natesampillai and Bren, {Gary D.} and Jaromir Sykora and Henning Walczak and Badley, {Andrew David}",
year = "2011",
doi = "10.1371/journal.pone.0027171",
language = "English (US)",
volume = "6",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "11",

}

TY - JOUR

T1 - TRAIL Dependent Fratricidal Killing of gp120 Primed Hepatocytes by HCV Core Expressing Hepatocytes

AU - Rizza, Stacey

AU - Challagundla, Kishore B.

AU - Natesampillai, Sekar

AU - Bren, Gary D.

AU - Sykora, Jaromir

AU - Walczak, Henning

AU - Badley, Andrew David

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84858756358&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84858756358&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0027171

DO - 10.1371/journal.pone.0027171

M3 - Article

C2 - 22110611

AN - SCOPUS:84858756358

VL - 6

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 11

M1 - e27171

ER -