2022
The In Vivo and In Vitro Architecture of the Hepatitis C Virus RNA Genome Uncovers Functional RNA Secondary and Tertiary Structures
Wan H, Adams RL, Lindenbach BD, Pyle AM. The In Vivo and In Vitro Architecture of the Hepatitis C Virus RNA Genome Uncovers Functional RNA Secondary and Tertiary Structures. Journal Of Virology 2022, 96: e01946-21. PMID: 35353000, PMCID: PMC9044954, DOI: 10.1128/jvi.01946-21.Peer-Reviewed Original ResearchConceptsSecondary structure mapRNA genomeRNA structureTertiary structureProtein-coding genesPositive-strand RNA virusesRegulatory RNA structuresFull-length structureHCV RNA genomeValuable model systemRNA structural motifsSecondary structural elementsEvolutionary functional analysisLife cycleVirus life cycleCellular contextCorresponding transcriptsImportant human pathogenLong RNAsGenomeSame RNAGenomic RNAComprehensive atlasFunctional analysisFunctional importance
2021
Restriction of SARS-CoV-2 replication by targeting programmed −1 ribosomal frameshifting
Sun Y, Abriola L, Niederer RO, Pedersen SF, Alfajaro MM, Silva Monteiro V, Wilen CB, Ho YC, Gilbert WV, Surovtseva YV, Lindenbach BD, Guo JU. Restriction of SARS-CoV-2 replication by targeting programmed −1 ribosomal frameshifting. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2023051118. PMID: 34185680, PMCID: PMC8256030, DOI: 10.1073/pnas.2023051118.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 replicationSARS-CoV-2Severe acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Syndrome coronavirus 2Vero E6 cellsHigh-throughput compound screenOpen reading frame 1bEffective antiviral strategiesCoronavirus 2E6 cellsAntiviral strategiesViral gene expressionCompound screenFluoroquinolone antibacterialsFrame 1bGene expression
2016
The Coding Region of the HCV Genome Contains a Network of Regulatory RNA Structures
Pirakitikulr N, Kohlway A, Lindenbach BD, Pyle AM. The Coding Region of the HCV Genome Contains a Network of Regulatory RNA Structures. Molecular Cell 2016, 62: 111-120. PMID: 26924328, PMCID: PMC4826301, DOI: 10.1016/j.molcel.2016.01.024.Peer-Reviewed Original ResearchConceptsRNA structureRegulatory RNA structuresComparative sequence analysisStructural RNA motifsRNA structure modelingLife cycleVirus life cycleRNA motifsPrimary sequenceCoding regionsGenomeBiological processesChemical probingSequence analysisRegulatory roleTertiary structureConformational changesVirus genomeFunctional assaysVersatile macromoleculesSpecific stagesStructure modelingFunctional informationMotifC virus genome
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
2005
Unravelling hepatitis C virus replication from genome to function
Lindenbach BD, Rice CM. Unravelling hepatitis C virus replication from genome to function. Nature 2005, 436: 933-938. PMID: 16107832, DOI: 10.1038/nature04077.Peer-Reviewed Original ResearchComplete 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 ResearchConceptsNonstructural protein 1Genetic interactionsRNA replicationViral RNA replicationGenetic screenSuppressor mutantsExtracytoplasmic compartmentsReplicase functionCytoplasmic complexDeletion mutantsReplicase componentsSingle mutationYellow fever virusProtein 1Additional mutationsNS1 geneRelated virusesInfected cellsIndependent selectionNS4A genesMutantsMutationsGenesReplicationDengue virus
1998
Noncytopathic Sindbis virus RNA vectors for heterologous gene expression
Agapov E, Frolov I, Lindenbach B, Prágai B, Schlesinger S, Rice C. Noncytopathic Sindbis virus RNA vectors for heterologous gene expression. Proceedings Of The National Academy Of Sciences Of The United States Of America 1998, 95: 12989-12994. PMID: 9789028, PMCID: PMC23682, DOI: 10.1073/pnas.95.22.12989.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBeta-GalactosidaseCell LineCloning, MolecularCricetinaeDNA-Directed RNA PolymerasesElectroporationGenes, ReporterGenetic VectorsGreen Fluorescent ProteinsKidneyLuminescent ProteinsPlasmidsRecombinant ProteinsRepliconRNA, ViralSindbis VirusTranscription, GeneticTransfectionViral ProteinsConceptsForeign gene expressionGene expressionLong-term foreign gene expressionSindbis vectorsHeterologous gene expressionDefective interfering genomesVirus-encoded genesHost protein synthesisVertebrate cellsHeterologous genesRecombinant Sindbis virusForeign genesDrug puromycinCellular metabolismProtein synthesisDNA transfectionRNA vectorSubgenomic transcriptsForeign proteinsRapid expressionBHK cellsGenesRepliconSindbis virusDramatic inhibition
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