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 ResearchConceptsTM 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
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 role
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