2014
Dynamic expression profiling of type I and type III interferon‐stimulated hepatocytes reveals a stable hierarchy of gene expression
Bolen CR, Ding S, Robek MD, Kleinstein SH. Dynamic expression profiling of type I and type III interferon‐stimulated hepatocytes reveals a stable hierarchy of gene expression. Hepatology 2014, 59: 1262-1272. PMID: 23929627, PMCID: PMC3938553, DOI: 10.1002/hep.26657.Peer-Reviewed Original ResearchConceptsGene expressionExpression profilingIndividual interferonMicroarray-based gene expression profilingDynamic expression profilingGene expression profilingSimilar signaling cascadesPotential specific rolesPromoter analysisTranscriptional responseHuh7 hepatoma cellsGene inductionExpression hierarchySignaling cascadesIFN-α signalingAntiviral stateNegative feedback mechanismType IPrimary human hepatocytesHepatoma cellsISG inductionSpecific roleGenesInterferon-stimulated gene inductionSuperior clinical activity
2012
Impaired Toll-Like Receptor 3-Mediated Immune Responses from Macrophages of Patients Chronically Infected with Hepatitis C Virus
Qian F, Bolen CR, Jing C, Wang X, Zheng W, Zhao H, Fikrig E, Bruce RD, Kleinstein SH, Montgomery RR. Impaired Toll-Like Receptor 3-Mediated Immune Responses from Macrophages of Patients Chronically Infected with Hepatitis C Virus. MSphere 2012, 20: 146-155. PMID: 23220997, PMCID: PMC3571267, DOI: 10.1128/cvi.00530-12.Peer-Reviewed Original ResearchMeSH KeywordsAdultFemaleGene ExpressionGenotypeHepacivirusHepatitis C, ChronicHumansInflammationInterferon-betaInterferonsInterleukinsLeukocytes, MononuclearMacrophagesMalePhosphorylationPolymorphism, Single NucleotideSignal TransductionSTAT1 Transcription FactorToll-Like Receptor 3Tumor Necrosis Factor-alphaViral LoadConceptsToll-like receptor 3Peripheral blood mononuclear cellsHepatitis C virusImmune responseHCV patientsC virusExpression of TLR3Clearance of HCVCommon chronic blood-borne infectionElevated innate immune responseImpaired toll-like receptorPrimary macrophagesHCV genotype 1Ongoing inflammatory responseMajority of patientsBlood-borne infectionsBlood mononuclear cellsToll-like receptorsIFN response genesPotential therapeutic approachInnate immune responseMacrophages of patientsElevated baseline expressionTLR3 pathwayViral clearance
2010
Lambda and alpha interferons inhibit hepatitis B virus replication through a common molecular mechanism but with different in vivo activities
Pagliaccetti NE, Chu EN, Bolen CR, Kleinstein SH, Robek MD. Lambda and alpha interferons inhibit hepatitis B virus replication through a common molecular mechanism but with different in vivo activities. Virology 2010, 401: 197-206. PMID: 20303135, PMCID: PMC2864496, DOI: 10.1016/j.virol.2010.02.022.Peer-Reviewed Original ResearchConceptsIFN-alpha/betaIFN-lambdaHepatitis B virus replicationB virus replicationType III interferonsRelated cytokines interleukinWeak antiviral activityHBV responseHBV replicationIL-22IL-6Molecular mechanismsCytokines interleukinAlpha interferonAntiviral immunityIII interferonsTransgenic miceAntiviral responseAntiviral mechanismAntiviral activityVirus replicationUnique receptorCommon molecular mechanismIFN-lambda2Vivo activity
2008
Interleukin-29 Functions Cooperatively with Interferon to Induce Antiviral Gene Expression and Inhibit Hepatitis C Virus Replication*
Pagliaccetti NE, Eduardo R, Kleinstein SH, Mu XJ, Bandi P, Robek MD. Interleukin-29 Functions Cooperatively with Interferon to Induce Antiviral Gene Expression and Inhibit Hepatitis C Virus Replication*. Journal Of Biological Chemistry 2008, 283: 30079-30089. PMID: 18757365, PMCID: PMC2662072, DOI: 10.1074/jbc.m804296200.Peer-Reviewed Original ResearchConceptsAntiviral gene expressionIFN-alpha/betaIL-29IFN-alphaVirus replicationIFN-gammaInhibits Hepatitis C Virus ReplicationCritical innate immune responseAntiviral activityHepatitis C virus replicationChronic viral infectionsC virus replicationGreater antiviral activityInnate immune responseIFN-gamma combinationHepatitis CGene expressionCellular antiviral responseCytokines interleukinHCV replicationImmune responseViral infectionIndividual cytokinesVesicular stomatitis virusAntiviral response