2015
Hepatitis C Virus RNA Replication Depends on Specific Cis- and Trans-Acting Activities of Viral Nonstructural Proteins
Kazakov T, Yang F, Ramanathan HN, Kohlway A, Diamond MS, Lindenbach BD. Hepatitis C Virus RNA Replication Depends on Specific Cis- and Trans-Acting Activities of Viral Nonstructural Proteins. PLOS Pathogens 2015, 11: e1004817. PMID: 25875808, PMCID: PMC4395149, DOI: 10.1371/journal.ppat.1004817.Peer-Reviewed Original ResearchConceptsRNA bindingRNA replicationPositive-strand RNA virus replicationComplementation group analysisPositive-strand RNA virusesPolymerase activityRNA virus replicationNS3 helicase domainViral nonstructural proteinsCis-acting roleGene functionVirus RNA replicationHelicase domainSpecific cisReplicase geneGenome replicationReplicase assemblyLethal mutationsNonstructural genesNTPase activityStudy of cisNonstructural proteinsRNA virusesSynthetic mRNAFunctional linkage
2013
Hepatitis C Virus RNA Replication and Virus Particle Assembly Require Specific Dimerization of the NS4A Protein Transmembrane Domain
Kohlway A, Pirakitikulr N, Barrera FN, Potapova O, Engelman DM, Pyle AM, Lindenbach BD. Hepatitis C Virus RNA Replication and Virus Particle Assembly Require Specific Dimerization of the NS4A Protein Transmembrane Domain. Journal Of Virology 2013, 88: 628-642. PMID: 24173222, PMCID: PMC3911751, DOI: 10.1128/jvi.02052-13.Peer-Reviewed Original ResearchMeSH KeywordsBase SequenceCell LineDimerizationDNA PrimersHepacivirusMembrane ProteinsModels, MolecularMutagenesis, Site-DirectedRNA, ViralViral Nonstructural ProteinsVirus AssemblyConceptsTM domainVirus particle assemblyRNA replicationTransmembrane protein essentialProtein transmembrane domainProtein-protein interactionsProtein interaction systemForward geneticsVirus RNA replicationParticle assemblySpecific dimerizationTransmembrane domainHuman blood group antigensProtein essentialTM helicesMutational effectsHomotypic interactionsDimer interfacePotential dimerizationTM interactionsVirus assemblyNonstructural proteinsDimeric interactionsHepatitis C Virus RNA ReplicationMutations
2011
Trafficking of Hepatitis C Virus Core Protein during Virus Particle Assembly
Counihan NA, Rawlinson SM, Lindenbach BD. Trafficking of Hepatitis C Virus Core Protein during Virus Particle Assembly. PLOS Pathogens 2011, 7: e1002302. PMID: 22028650, PMCID: PMC3197604, DOI: 10.1371/journal.ppat.1002302.Peer-Reviewed Original ResearchMeSH KeywordsHEK293 CellsHepacivirusHumansLipidsMicroscopy, ConfocalMicrotubulesViral Core ProteinsViral Nonstructural ProteinsVirus Assembly
2010
Hepatitis C Virus NS2 Coordinates Virus Particle Assembly through Physical Interactions with the E1-E2 Glycoprotein and NS3-NS4A Enzyme Complexes
Stapleford KA, Lindenbach BD. Hepatitis C Virus NS2 Coordinates Virus Particle Assembly through Physical Interactions with the E1-E2 Glycoprotein and NS3-NS4A Enzyme Complexes. Journal Of Virology 2010, 85: 1706-1717. PMID: 21147927, PMCID: PMC3028914, DOI: 10.1128/jvi.02268-10.Peer-Reviewed Original ResearchConceptsProtein complexesBlue native polyacrylamide gel electrophoresisEnzyme complexHepatitis C virus NS2Early secretory pathwayProtein complex formationHepatitis C Virus NS2 ProteinViral proteinsNative polyacrylamide gel electrophoresisParticle assemblyHCV particle assemblyVirus particle assemblyGenetic interactionsSecretory pathwayComplex interactsCentral organizing roleInteraction partnersE1-E2 glycoproteinsNS2 proteinVirus assemblyNonstructural proteinsPolyacrylamide gel electrophoresisP7 proteinProteinOrganizing roleThe Acidic Domain of Hepatitis C Virus NS4A Contributes to RNA Replication and Virus Particle Assembly
Phan T, Kohlway A, Dimberu P, Pyle AM, Lindenbach BD. The Acidic Domain of Hepatitis C Virus NS4A Contributes to RNA Replication and Virus Particle Assembly. Journal Of Virology 2010, 85: 1193-1204. PMID: 21047963, PMCID: PMC3020511, DOI: 10.1128/jvi.01889-10.Peer-Reviewed Original ResearchConceptsVirus particle assemblyAcidic domainGenome replicationAssembly defectsEnzyme complexSevere defectsMembrane-bound enzyme complexRNA replicationTerminal acidic domainNS3-4AAlanine-scanning mutagenesisSecond-site mutationsViral genome replicationHepatitis C virus (HCV) NS3-4AGenetic interactionsRNA helicaseParticle assemblyReplication defectScanning mutagenesisMutant formsVirus assemblySerine proteasesEnzymatic activityATPase activityMutants
2009
Hepatitis C Virus NS2 Protein Contributes to Virus Particle Assembly via Opposing Epistatic Interactions with the E1-E2 Glycoprotein and NS3-NS4A Enzyme Complexes
Phan T, Beran RK, Peters C, Lorenz IC, Lindenbach BD. Hepatitis C Virus NS2 Protein Contributes to Virus Particle Assembly via Opposing Epistatic Interactions with the E1-E2 Glycoprotein and NS3-NS4A Enzyme Complexes. Journal Of Virology 2009, 83: 8379-8395. PMID: 19515772, PMCID: PMC2738163, DOI: 10.1128/jvi.00891-09.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAmino Acid SubstitutionCarrier ProteinsHepacivirusHumansIntracellular Signaling Peptides and ProteinsModels, MolecularMolecular Sequence DataMutation, MissenseProtein BindingProtein Interaction MappingSuppression, GeneticViral Envelope ProteinsViral Nonstructural ProteinsViral ProteinsVirus AssemblyConceptsHepatitis C Virus NS2 ProteinVirus particle assemblyNS2 proteinVirus assemblyReverse genetic analysisForward genetic selectionSecond-site mutationsNS2 mutantsSuppressor mutationsRNA bindingEpistatic interactionsBiochemical experimentsGenetic analysisEnzyme complexSevere defectsNonstructural proteinsGenetic selectionParticle assemblyRNA replicationCell culture systemMutationsNS3-NS4AProteinMutantsMutual exclusivity
2005
Complete Replication of Hepatitis C Virus in Cell Culture
Lindenbach BD, Evans MJ, Syder AJ, Wölk B, Tellinghuisen TL, Liu CC, Maruyama T, Hynes RO, Burton DR, McKeating JA, Rice CM. Complete Replication of Hepatitis C Virus in Cell Culture. Science 2005, 309: 623-626. PMID: 15947137, DOI: 10.1126/science.1114016.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntibodies, ViralAntigens, CDAntiviral AgentsCell Line, TumorCentrifugation, Density GradientCulture Media, ConditionedGenome, ViralHepacivirusHumansInterferon-alphaMutationNeutralization TestsRepliconRNA, ViralSerial PassageTetraspanin 28TransfectionViral Envelope ProteinsViral Nonstructural ProteinsVirionVirus CultivationVirus ReplicationConceptsHepatitis C virus (HCV) life cyclePutative HCV receptorFull-length HCV genomeHepatitis C virusViral glycoprotein E2Cell culturesVirus particlesHCV receptorsC virusVirus life cycleHCV genomeGlycoprotein E2Important human pathogenAntiviral compoundsImproved antiviralsViral entryMonoclonal antibodiesCellular expressionInfectious unitsHuman pathogensVitro systemHCVccAntiviralsReplication
1999
Genetic Interaction of Flavivirus Nonstructural Proteins NS1 and NS4A as a Determinant of Replicase Function
Lindenbach B, Rice C. Genetic Interaction of Flavivirus Nonstructural Proteins NS1 and NS4A as a Determinant of Replicase Function. Journal Of Virology 1999, 73: 4611-4621. PMID: 10233920, PMCID: PMC112502, DOI: 10.1128/jvi.73.6.4611-4621.1999.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCell LineCricetinaeMolecular Sequence DataRNA-Dependent RNA PolymeraseRNA, ViralViral Nonstructural ProteinsYellow fever virusConceptsNonstructural protein 1Genetic interactionsRNA replicationViral RNA replicationGenetic screenSuppressor mutantsExtracytoplasmic compartmentsReplicase functionCytoplasmic complexDeletion mutantsReplicase componentsSingle mutationYellow fever virusProtein 1Additional mutationsNS1 geneRelated virusesInfected cellsIndependent selectionNS4A genesMutantsMutationsGenesReplicationDengue virus
1997
trans-Complementation of yellow fever virus NS1 reveals a role in early RNA replication
Lindenbach B, Rice C. trans-Complementation of yellow fever virus NS1 reveals a role in early RNA replication. Journal Of Virology 1997, 71: 9608-9617. PMID: 9371625, PMCID: PMC230269, DOI: 10.1128/jvi.71.12.9608-9617.1997.Peer-Reviewed Original Research
1994
Processing in the hepatitis C virus E2-NS2 region: identification of p7 and two distinct E2-specific products with different C termini
Lin C, Lindenbach B, Prágai B, McCourt D, Rice C. Processing in the hepatitis C virus E2-NS2 region: identification of p7 and two distinct E2-specific products with different C termini. Journal Of Virology 1994, 68: 5063-5073. PMID: 7518529, PMCID: PMC236449, DOI: 10.1128/jvi.68.8.5063-5073.1994.Peer-Reviewed Original Research