2013
Deep Sequencing Analysis of HCV NS3 Resistance-Associated Variants and Mutation Linkage in Liver Transplant Recipients
Kirst M, Li E, Wang C, Dong H, Liu C, Fried M, Nelson D, Wang G. Deep Sequencing Analysis of HCV NS3 Resistance-Associated Variants and Mutation Linkage in Liver Transplant Recipients. PLOS ONE 2013, 8: e69698. PMID: 23922778, PMCID: PMC3726766, DOI: 10.1371/journal.pone.0069698.Peer-Reviewed Original ResearchConceptsResistance-associated variantsProtease inhibitorsChronic HCV infectionLiver transplant recipientsHCV drug resistanceFuture therapeutic strategiesHCV protease inhibitorsMutation linkageHigh-level resistanceLow levelsPI monotherapyTransplant recipientsHCV infectionLiver transplantLiver transplantationAntiviral therapyHCV populationTherapeutic strategiesViral variantsDrug resistanceDecreased susceptibilityQuasispecies populationPatientsDominant variantDeep sequencing analysis
2012
Iron Regulator Hepcidin Exhibits Antiviral Activity against Hepatitis C Virus
Liu H, Le Trinh T, Dong H, Keith R, Nelson D, Liu C. Iron Regulator Hepcidin Exhibits Antiviral Activity against Hepatitis C Virus. PLOS ONE 2012, 7: e46631. PMID: 23110054, PMCID: PMC3478283, DOI: 10.1371/journal.pone.0046631.Peer-Reviewed Original ResearchConceptsHCV infectionHepcidin expressionSerious chronic liver diseaseAntiviral activityHepatitis C viral infectionHepcidin expression levelsChronic HCV infectionChronic liver diseaseC viral infectionHepatitis C virusDirect antiviral activityIntracellular antiviral stateHepatocellular carcinoma progressionInnate antiviral defenseLiver diseaseC virusAntiviral effectHCV replicationIron overloadHepatocellular carcinomaExhibit antiviral activityHCVViral infectionSuppressive effectAmino acid peptideNanoparticle-based artificial RNA silencing machinery for antiviral therapy
Wang Z, Liu H, Yang S, Wang T, Liu C, Cao Y. Nanoparticle-based artificial RNA silencing machinery for antiviral therapy. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 12387-12392. PMID: 22802676, PMCID: PMC3412013, DOI: 10.1073/pnas.1207766109.Peer-Reviewed Original ResearchConceptsFundamental gene regulatory mechanismsHepatitis C virusGene regulatory mechanismsCultured cellsTarget RNA cleavageSequence-specific mannerCellular interferon responseFunctional genomicsHuman hepatoma cellsRNA interferenceArtificial RNARegulatory mechanismsMouse modelRNA cleavageCultured human hepatoma cellsSpecific mannerHCV RNA levelsRNAXenotransplantation mouse modelHepatoma cellsInterferon responsePotent antiviral activityRNA levelsMachineryProteinase activity
2011
Expression of an IRF-3 fusion protein and mouse estrogen receptor, inhibits hepatitis C viral replication in RIG-I-deficient Huh 7.5 cells
Yao L, Yan X, Dong H, Nelson D, Liu C, Li X. Expression of an IRF-3 fusion protein and mouse estrogen receptor, inhibits hepatitis C viral replication in RIG-I-deficient Huh 7.5 cells. Virology Journal 2011, 8: 445. PMID: 21936899, PMCID: PMC3213043, DOI: 10.1186/1743-422x-8-445.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineDEAD Box Protein 58DEAD-box RNA HelicasesGene ExpressionHepacivirusHepatocytesHumansInterferon Regulatory Factor-3Interferon-alphaInterferon-betaMiceProtein BiosynthesisProtein MultimerizationReal-Time Polymerase Chain ReactionReceptors, EstrogenReceptors, ImmunologicRecombinant Fusion ProteinsTranscription, GeneticVirus ReplicationConceptsAnti-HCV effectInterferon regulatory factor 3Huh-7.5 cellsEstrogen receptorPolymerase chain reactionHepatitis C virus infectionViral replicationC virus infectionMouse estrogen receptorHepatitis C viral replicationInterferon-stimulated gene expressionExpression of IFNHCV viral replicationHCV RNA replicationReal-time polymerase chain reactionEstrogen receptor agonistsExpression of ISGsRegulatory factor 3HCV IRES-dependent translationCharacterization of HCV Interactions with Toll-Like Receptors and RIG-I in Liver Cells
Eksioglu E, Zhu H, Bayouth L, Bess J, Liu H, Nelson D, Liu C. Characterization of HCV Interactions with Toll-Like Receptors and RIG-I in Liver Cells. PLOS ONE 2011, 6: e21186. PMID: 21695051, PMCID: PMC3117876, DOI: 10.1371/journal.pone.0021186.Peer-Reviewed Original ResearchMeSH KeywordsCell DeathCell Line, TumorDEAD Box Protein 58DEAD-box RNA HelicasesDown-RegulationHepacivirusHost-Pathogen InteractionsHumansInterferon-betaLiverProtein BindingReceptors, ImmunologicSignal TransductionTNF-Related Apoptosis-Inducing LigandToll-Like ReceptorsViral Envelope ProteinsVirus ReplicationConceptsHuh7.5 cellsViral replicationHCV chronic patientsExpression of TLR3Toll-like receptorsHCV envelope proteinsExpression levelsRIG-I expressionHCV interactionChronic patientsHCVTRAIL pathwayViral escapeViral infectionInnate immunityViral pathogenesisTLR3Induction of apoptosisAntiviral stateIFN inductionLow expression levelsLiver cellsLH86Envelope proteinIFNIdentification of the IFITM3 gene as an inhibitor of hepatitis C viral translation in a stable STAT1 cell line
Yao L, Dong H, Zhu H, Nelson D, Liu C, Lambiase L, Li X. Identification of the IFITM3 gene as an inhibitor of hepatitis C viral translation in a stable STAT1 cell line. Journal Of Viral Hepatitis 2011, 18: e523-e529. PMID: 21914072, PMCID: PMC3736357, DOI: 10.1111/j.1365-2893.2011.01452.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarrier ProteinsCell LineGene ExpressionHepacivirusHumansMembrane ProteinsMiceProtein BiosynthesisProtein MultimerizationReal-Time Polymerase Chain ReactionReceptors, EstrogenRecombinant Fusion ProteinsRNA, ViralRNA-Binding ProteinsSTAT1 Transcription FactorTamoxifenTranscriptional ActivationViral ProteinsConceptsFusion proteinCell linesRNA replicationInterferon-induced transmembrane protein 3Internal ribosomal entry siteHCV IRESHCV internal ribosomal entry siteTransmembrane protein 3HCV RNA replicationMouse estrogen receptorSignal transducerTranscription 1Gene expressionViral translationIFITM3 geneHuh7.5 cell lineReal-time PCRAnti-HCV effectGenesEntry siteElevated expressionProtein 3Western blottingIRESProtein
2009
Hepatitis C virus modulates human monocyte‐derived dendritic cells
Eksioglu E, Bess J, Zhu H, Xu Y, Dong H, Elyar J, Nelson D, Liu C. Hepatitis C virus modulates human monocyte‐derived dendritic cells. Journal Of Viral Hepatitis 2009, 17: 757-769. PMID: 20051006, PMCID: PMC3731759, DOI: 10.1111/j.1365-2893.2009.01231.x.Peer-Reviewed Original ResearchConceptsHepatitis C virusNewcastle disease virusHCV infectionC virusHuman monocyte-derived dendritic cellsViral titresMonocyte-derived dendritic cellsType 1 IFN responseFlow cytometryType 1 interferon responseMaturation of DCsDendritic cell responsesReal-time reverse transcriptase-polymerase chain reactionReverse transcriptase-polymerase chain reactionTranscriptase-polymerase chain reactionHuh-7.5 cellsDC numbersDendritic cellsImmature DCsIFNβ expressionJFH-1Control monocytesHost immunityViral evasionIFN responseFocal Distribution of Hepatitis C Virus RNA in Infected Livers
Stiffler J, Nguyen M, Sohn J, Liu C, Kaplan D, Seeger C. Focal Distribution of Hepatitis C Virus RNA in Infected Livers. PLOS ONE 2009, 4: e6661. PMID: 19688046, PMCID: PMC2722721, DOI: 10.1371/journal.pone.0006661.Peer-Reviewed Original ResearchMeSH KeywordsBlotting, WesternCohort StudiesGene DosageHepacivirusHepatitis CHumansInterferonsLiverRNA, ViralConceptsHepatitis C virusHCV RNA levelsHCV RNAHCV replicationRNA levelsBiopsy samplesHCV RNA copy numbersIntrahepatic HCV-RNA levelsISG levelsHepatitis C virus RNAWhole liver sectionsC virus RNAViral RNA levelsFocal distributionInnate immune responseRNA copy numberHCV infectionC virusInfected patientsInfected hepatocytesInterferon betaImmune responseInfected liverLiver sectionsIFNbeta expressionPrimary Human Hepatocyte Culture for HCV Study
Zhu H, Elyar J, Foss R, Hemming A, Hall E, LeCluyse E, Liu C. Primary Human Hepatocyte Culture for HCV Study. Methods In Molecular Biology 2009, 510: 373-382. PMID: 19009276, DOI: 10.1007/978-1-59745-394-3_28.Peer-Reviewed Original ResearchConceptsHuman primary hepatocytesAntiviral researchPrimary hepatocyte culturesHuman primary hepatocyte culturesSmall animal modelsPrimary hepatocytesHepatocyte culturesPrimary human hepatocyte culturesHCV infectionHCV pathogenesisLiver perfusionHuman hepatocyte culturesHCV researchHost-virus interactionsInfectious virusHCV studiesPrimary culturesCell model systemHepatocyte isolationHepatocytesJFH1PathogenesisPerfusionInfection
2007
Hepatitis C Virus Triggers Apoptosis of a Newly Developed Hepatoma Cell Line Through Antiviral Defense System
Zhu H, Dong H, Eksioglu E, Hemming A, Cao M, Crawford J, Nelson D, Liu C. Hepatitis C Virus Triggers Apoptosis of a Newly Developed Hepatoma Cell Line Through Antiviral Defense System. Gastroenterology 2007, 133: 1649-1659. PMID: 17983809, DOI: 10.1053/j.gastro.2007.09.017.Peer-Reviewed Original ResearchConceptsTumor necrosis factor-related apoptosis-inducing ligandHCV infectionViral infectionHepatoma cell lineHCV isolatesJFH-1New hepatoma cell lineViral replicationCell linesMechanisms of HCVAcute HCV infectionChronic viral infectionsPathogenesis of HCVNovel human hepatoma cell lineInterferon response factor 3Antiviral defense systemNecrosis factor-related apoptosis-inducing ligandType I interferon inductionFactor-related apoptosis-inducing ligandExpression of interferonHost immune systemHepatocellular carcinoma tissuesI interferon inductionDeath receptor 5Induction of interferon
2005
Novel type I interferon IL-28A suppresses hepatitis C viral RNA replication
Zhu H, Butera M, Nelson D, Liu C. Novel type I interferon IL-28A suppresses hepatitis C viral RNA replication. Virology Journal 2005, 2: 80. PMID: 16146571, PMCID: PMC1232870, DOI: 10.1186/1743-422x-2-80.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntiviral AgentsBase SequenceCell LineGenes, MHC Class IHepacivirusHepatitis CHumansInterferon Regulatory Factor-1Interferon Type IInterferon-alphaInterferon-Stimulated Gene Factor 3Interleukin-10InterleukinsJanus KinasesMolecular Sequence DataRNA, ViralSignal TransductionSTAT Transcription FactorsVirus ReplicationConceptsInterferon-stimulated genesIL-28AAntiviral activityAntiviral efficacyHuman hepatoma cellsSide effectsChronic hepatitis C viral infectionHepatitis C viral infectionViral RNA replicationAntiviral response ratesHCV subgenomic RNA replicationIFNα-based therapyGenotype 1 infectionHCV chronic infectionC viral infectionIL-10 receptorIL-10 treatmentHLA class IType I IFNJAK-STATRNA replicationDose-dependent mannerHepatoma cellsExpression of ISGsUndesirable side effectsDefective Jak-Stat Activation in Hepatoma Cells Is Associated with Hepatitis C Viral IFN- Resistance
Zhu H, Nelson D, Crawford J, Liu C. Defective Jak-Stat Activation in Hepatoma Cells Is Associated with Hepatitis C Viral IFN- Resistance. Journal Of Interferon & Cytokine Research 2005, 25: 528-539. PMID: 16181053, DOI: 10.1089/jir.2005.25.528.Peer-Reviewed Original ResearchMeSH KeywordsAntiviral AgentsCarcinoma, HepatocellularCell Line, TumorDNA-Binding ProteinsDrug Resistance, ViralHepacivirusHumansInterferon-alphaLiverLiver NeoplasmsMutationProtein-Tyrosine KinasesRepliconRepressor ProteinsSTAT3 Transcription FactorSuppressor of Cytokine Signaling 3 ProteinSuppressor of Cytokine Signaling ProteinsTrans-ActivatorsTranscription FactorsViral Nonstructural ProteinsConceptsIFN resistanceHCV subgenomic replicon cell culture systemViral infectionChronic hepatitis C viral infectionIFN-sensitive cell linesHepatitis C viral infectionIFN stimulationCell linesRibavirin combination therapyMajority of patientsC viral infectionSTAT3 activationResistant cell linesIFN monotherapyIFN therapySuppressor of cytokineCombination therapyIFN sensitivityJAK-STAT activationIFNPotential mechanismsLong-term cultureCell culture systemExhibit alterationsJAK-STATCyclosporine suppresses hepatitis C virus in vitro and increases the chance of a sustained virological response after liver transplantation
Firpi R, Zhu H, Morelli G, Abdelmalek M, Soldevila‐Pico C, Machicao V, Cabrera R, Reed A, Liu C, Nelson D. Cyclosporine suppresses hepatitis C virus in vitro and increases the chance of a sustained virological response after liver transplantation. Liver Transplantation 2005, 12: 51-57. PMID: 16382464, DOI: 10.1002/lt.20532.Peer-Reviewed Original ResearchConceptsLiver transplant recipientsSustained virological responseVirological responseTransplant recipientsCombination of cyclosporineInterferon-based therapyCombination of interferonEffect of cyclosporineDose-dependent mannerAnti-viral potentialLiver transplantationHistologic diseaseImmunosuppressive agentsViral clearanceHerpes simplexC virusAntiviral effectCyclosporine inhibitsCyclosporineTherapyViral replicationAntiviral activityTacrolimusInterferonReplicon system
2004
STAT3 induces anti-hepatitis C viral activity in liver cells
Zhu H, Shang X, Terada N, Liu C. STAT3 induces anti-hepatitis C viral activity in liver cells. Biochemical And Biophysical Research Communications 2004, 324: 518-528. PMID: 15474458, DOI: 10.1016/j.bbrc.2004.09.081.Peer-Reviewed Original ResearchMeSH KeywordsAntiviral AgentsBlotting, NorthernBlotting, WesternCarcinoma, HepatocellularCell LineCell Line, TumorCytokinesDNA-Binding ProteinsDose-Response Relationship, DrugEnzyme InhibitorsGenes, DominantHepacivirusHumansInflammationInterferonsInterleukin-6LigandsLiverLiver NeoplasmsLuciferasesPlasmidsProtein Structure, TertiaryReverse Transcriptase Polymerase Chain ReactionRibavirinRNARNA, MessengerSTAT3 Transcription FactorTime FactorsTrans-ActivatorsTransfectionTyrphostinsConceptsAnti-HCV activityInterferon alphaSTAT3 activationHuman hepatoma cellsHepatitis C virus infectionHCV subgenomic RNA replicationMain therapeutic regimenC virus infectionChronic liver diseaseCytokines IL-6Replicon cell linesIntracellular antiviral stateCell linesHepatoma cellsLiver diseaseTherapeutic regimenActivation of STAT3IL-6Virus infectionEstrogen receptorIFN treatmentAntiviral genesAntiviral pathwaysAntiviral activityAntiviral stateSustained viral response to interferon and ribavirin in liver transplant recipients with recurrent hepatitis C
Abdelmalek M, Firpi R, Soldevila‐Pico C, Reed A, Hemming A, Liu C, Crawford J, Davis G, Nelson D. Sustained viral response to interferon and ribavirin in liver transplant recipients with recurrent hepatitis C. Liver Transplantation 2004, 10: 199-207. PMID: 14762857, DOI: 10.1002/lt.20074.Peer-Reviewed Original ResearchConceptsHepatitis C virusLiver transplant recipientsTransplant recipientsHepatitis CLiver histologyFibrosis stageHCV RNAViral clearanceViral responseCombination therapyDetectable hepatitis C virusRecurrent chronic hepatitis CRecurrent hepatitis C infectionRecurrent hepatitis C virusDetectable HCV RNASustained viral responseChronic hepatitis CInterferon-based treatmentOrthotopic liver transplantationRecurrent hepatitis CHepatitis C infectionInterferon-based therapyRegression of fibrosisGrade of inflammationBaseline histology
2003
CD8+ T‐cell interaction with HCV replicon cells: Evidence for both cytokine‐ and cell‐mediated antiviral activity
Liu C, Zhu H, Tu Z, Xu Y, Nelson D. CD8+ T‐cell interaction with HCV replicon cells: Evidence for both cytokine‐ and cell‐mediated antiviral activity. Hepatology 2003, 37: 1335-1342. PMID: 12774012, DOI: 10.1053/jhep.2003.50207.Peer-Reviewed Original ResearchConceptsHepatitis C virusHCV replicon cellsAntiviral activityReplicon cellsHCV repliconMechanisms of HCVAnti-tumor necrosis factor alphaHCV subgenomic replicon systemAnti-interferon gammaDirect cytolytic effectHLA-A11 alleleNecrosis factor alphaHLA class IHost immune responseSubgenomic replicon systemT cell interactionsT-cell bindingHCV nonstructural proteinsCytolytic functionHCV interactionC virusSpecific lysisInfected hepatocytesTNF-alphaAntiviral effectGene expression associated with interferon alfa antiviral activity in an HCV replicon cell line
Zhu H, Zhao H, Collins C, Eckenrode S, Run Q, McIndoe R, Crawford J, Nelson D, She J, Liu C. Gene expression associated with interferon alfa antiviral activity in an HCV replicon cell line. Hepatology 2003, 37: 1180-1188. PMID: 12717400, DOI: 10.1053/jhep.2003.50184.Peer-Reviewed Original ResearchMeSH KeywordsAntiviral AgentsCarcinoma, HepatocellularDNA-Binding ProteinsGene ExpressionHepacivirusHepatitis C, ChronicHepatocytesHumansInterferon-alphaLiver NeoplasmsRNA, ViralSignal TransductionSTAT1 Transcription FactorSTAT3 Transcription FactorTrans-ActivatorsTumor Cells, CulturedViral ProteinsVirus ReplicationConceptsIFN-alpha antiviral activityIFN-alphaAntiviral activityReplicon cellsHCV replicon cell culture systemChronic hepatitis C viral infectionHepatitis C viral infectionHCV subgenomic RNA replicationHCV replicon cell linesC viral infectionOnly therapeutic optionDirect antiviral activityReplicon cell linesAnti-HCV activityHepatoma cellsDifferent gene expression profilesFeasible experimental modelIFN-alpha signalingCDNA microarray analysisGene expression profilesTherapeutic optionsActivation of STAT3Antiviral efficacyViral infectionResponsive genesInterleukin-1 Inhibits Hepatitis C Virus Subgenomic RNA Replication by Activation of Extracellular Regulated Kinase Pathway
Zhu H, Liu C. Interleukin-1 Inhibits Hepatitis C Virus Subgenomic RNA Replication by Activation of Extracellular Regulated Kinase Pathway. Journal Of Virology 2003, 77: 5493-5498. PMID: 12692250, PMCID: PMC153991, DOI: 10.1128/jvi.77.9.5493-5498.2003.Peer-Reviewed Original ResearchConceptsInterferon-stimulated genesHepatitis C virusInterleukin-1Antiviral activityHCV subgenomic RNA replicationDirect antiviral activityIL-1 productionReplicon cell linesNovel antiviral pathwayViral protein expressionViral clearanceC virusChronic infectionInflammatory processRNA replicationExtracellular-regulated kinase (ERK) pathwayAntiviral pathwaysInhibitory effectProtein expressionCell linesKinase pathwayKinase activationActivationPatientsInfection
2002
Combination of interferon alfa‐2b and ribavirin in liver transplant recipients with histological recurrent hepatitis C
Firpi R, Abdelmalek M, Soldevila‐Pico C, Reed A, Hemming A, Howard R, van der Werf W, Lauwers G, Liu C, Crawford J, Davis G, Nelson D. Combination of interferon alfa‐2b and ribavirin in liver transplant recipients with histological recurrent hepatitis C. Liver Transplantation 2002, 8: 1000-1006. PMID: 12424712, DOI: 10.1053/jlts.2002.34968.Peer-Reviewed Original ResearchConceptsInterferon alfa-2bLiver transplantationAlfa-2bHistological recurrenceViral eradicationHCV RNAWeek 24Recurrent hepatitis C virus (HCV) infectionHCV RNA 6 monthsHepatitis C virus infectionEnd pointProgressive cholestatic diseaseRecurrent HCV infectionSerum HCV RNAC virus infectionLiver transplant recipientsPrimary end pointRecurrent hepatitis CSecondary end pointsGenotype 1 infectionYears of therapyEnd of treatmentHigh viral loadLiver biopsy resultsRecurrent HCV