Please use this identifier to cite or link to this item:
Title: Hepatitis C virus-induced hepatocyte cell death and protection by inhibition of apoptosis.
Austin Authors: Lim, Eu Jin ;El Khobar, Korri;Chin, Ruth;Earnest-Silveira, Linda;Angus, Peter W ;Bock, C-Thomas;Nachbur, Ueli;Silke, John;Torresi, Joseph 
Affiliation: Medicine (University of Melbourne)
Walter and Eliza Hall Institute, Parkville, Victoria, Australia
Infectious Diseases
Department of Virology, Robert Koch Institute, Berlin, Germany.
Gastroenterology and Hepatology
Issue Date: 27-Jun-2014
Publication information: The Journal of General Virology 2014; 95(Pt 10): 2204-15
Abstract: Chronic hepatitis C virus (HCV) infection results in progressive liver fibrosis leading to cirrhosis and liver cancer. The mechanism for this remains unclear but hepatocyte apoptosis is thought to play a major role. Hepatocyte apoptosis in human liver tissue was determined by immunohistochemistry for cytokeratin 18 (M30 CytoDEATH) and cleaved poly(ADP-ribose) polymerase (PARP). In vitro studies were performed with replication-defective recombinant adenoviruses expressing HCV proteins (rAdHCV) to study the effects of HCV on cell death in Huh7 cells, primary mouse hepatocytes (PMoHs) and primary human hepatocytes (PHHs). Cell viability and apoptosis were studied using crystal violet assays and Western blots probed for cleaved caspase-3 and cleaved PARP, with and without treatment with the pan-caspase inhibitor Q-VD-OPh and necrostatin-1. Liver tissue of HCV-infected patients expressed elevated levels of apoptotic markers compared with HCV-negative patients. rAdHCV infection reduced cell viability compared with uninfected controls and cells infected with control virus (rAdGFP). Huh7, PMoHs and PHHs infected with rAdHCV showed significantly increased levels of apoptotic markers compared with uninfected controls and rAdGFP-infected cells. In rAdHCV-infected Huh7, treatment with Q-VD-OPh and necrostatin-1 both improved cell viability. Q-VD-Oph also reduced cleaved PARP in rAdHCV-infected Huh7 and PMoHs. Hepatocyte apoptosis is known to be increased in the livers of HCV-infected patients. HCV promoted cell death in primary and immortalized hepatocytes, and this was inhibited by Q-VD-OPh and necrostatin-1. These findings indicate that HCV-induced cell death occurs by both apoptosis and necroptosis, and provide new insights into the mechanisms of HCV-induced liver injury.
DOI: 10.1099/vir.0.065862-0
Journal: The Journal of General Virology
Type: Journal Article
Subjects: Amino Acid Chloromethyl Ketones.metabolism
Cell Survival
Enzyme Inhibitors.metabolism
Hepatitis C.pathology
Hepatocytes.drug effects.physiology.virology
Mice, Inbred C57BL
Appears in Collections:Journal articles

Show full item record

Page view(s)

checked on Jul 23, 2024

Google ScholarTM


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.