Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/12279
Full metadata record
DC FieldValueLanguage
dc.contributor.authorLim, Eu Jin-
dc.contributor.authorEl Khobar, Korri-
dc.contributor.authorChin, Ruth-
dc.contributor.authorEarnest-Silveira, Linda-
dc.contributor.authorAngus, Peter W-
dc.contributor.authorBock, C-Thomas-
dc.contributor.authorNachbur, Ueli-
dc.contributor.authorSilke, John-
dc.contributor.authorTorresi, Joseph-
dc.date.accessioned2015-05-16T01:56:27Z
dc.date.available2015-05-16T01:56:27Z
dc.date.issued2014-06-27-
dc.identifier.citationThe Journal of General Virology 2014; 95(Pt 10): 2204-15en_US
dc.identifier.otherPUBMEDen
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/12279en
dc.description.abstractChronic 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.en_US
dc.language.isoenen
dc.subject.otherAmino Acid Chloromethyl Ketones.metabolismen
dc.subject.otherAnimalsen
dc.subject.otherApoptosisen
dc.subject.otherCaspases.analysisen
dc.subject.otherCell Survivalen
dc.subject.otherEnzyme Inhibitors.metabolismen
dc.subject.otherHepacivirus.physiologyen
dc.subject.otherHepatitis C.pathologyen
dc.subject.otherHepatocytes.drug effects.physiology.virologyen
dc.subject.otherHumansen
dc.subject.otherImidazoles.metabolismen
dc.subject.otherIndoles.metabolismen
dc.subject.otherMiceen
dc.subject.otherMice, Inbred C57BLen
dc.subject.otherNecrosisen
dc.subject.otherQuinolines.metabolismen
dc.titleHepatitis C virus-induced hepatocyte cell death and protection by inhibition of apoptosis.en_US
dc.typeJournal Articleen_US
dc.identifier.journaltitleThe Journal of General Virologyen_US
dc.identifier.affiliationMedicine (University of Melbourne)en_US
dc.identifier.affiliationWalter and Eliza Hall Institute, Parkville, Victoria, Australiaen_US
dc.identifier.affiliationInfectious Diseasesen_US
dc.identifier.affiliationDepartment of Virology, Robert Koch Institute, Berlin, Germany.en_US
dc.identifier.affiliationGastroenterology and Hepatologyen_US
dc.identifier.doi10.1099/vir.0.065862-0en_US
dc.description.pages2204-15en
dc.relation.urlhttps://pubmed.ncbi.nlm.nih.gov/24973240en
dc.type.contentTexten_US
dc.type.austinJournal Articleen
local.name.researcherAngus, Peter W
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.fulltextNo Fulltext-
item.grantfulltextnone-
item.languageiso639-1en-
item.openairetypeJournal Article-
crisitem.author.deptVictorian Liver Transplant Unit-
crisitem.author.deptVictorian Liver Transplant Unit-
crisitem.author.deptGastroenterology and Hepatology-
crisitem.author.deptInfectious Diseases-
Appears in Collections:Journal articles
Show simple item record

Page view(s)

52
checked on Mar 28, 2024

Google ScholarTM

Check


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