Featured Publications
Reinventing positive-strand RNA virus reverse genetics
Lindenbach BD. Reinventing positive-strand RNA virus reverse genetics. Advances In Virus Research 2022, 112: 1-29. PMID: 35840179, PMCID: PMC9273853, DOI: 10.1016/bs.aivir.2022.03.001.Chapters
2023
Astrovirus replication is dependent on induction of double-membrane vesicles through a PI3K-dependent, LC3-independent pathway
Bub T, Hargest V, Tan S, Smith M, Vazquez-Pagan A, Flerlage T, Brigleb P, Meliopoulos V, Lindenbach B, Ramanathan H, Cortez V, Crawford J, Schultz-Cherry S. Astrovirus replication is dependent on induction of double-membrane vesicles through a PI3K-dependent, LC3-independent pathway. Journal Of Virology 2023, 97: e01025-23. PMID: 37668367, PMCID: PMC10537808, DOI: 10.1128/jvi.01025-23.Peer-Reviewed Original ResearchConceptsAstrovirus infectionAstrovirus replicationPromising therapeutic optionPositive-sense RNA virus infectionPotential antiviral targetsRNA virusesRNA virus infectionCritical new evidenceGastrointestinal symptomsTherapeutic optionsPositive-sense RNA virusesVirus infectionTherapeutic interventionsAntiviral targetViral replicationDMV formationInfectionGenetic inhibitionReplication organellesHuman astrovirusPI3KPotential targetEarly componentPatientsAutophagy machinery
2021
Placenta-derived interferon-stimulated gene 20 controls ZIKA virus infection
Ding J, Aldo P, Roberts CM, Stabach P, Liu H, You Y, Qiu X, Jeong J, Maxwell A, Lindenbach B, Braddock D, Liao A, Mor G. Placenta-derived interferon-stimulated gene 20 controls ZIKA virus infection. EMBO Reports 2021, 22: embr202152450. PMID: 34405956, PMCID: PMC8490983, DOI: 10.15252/embr.202152450.Peer-Reviewed Original ResearchMeSH KeywordsAntiviral AgentsExoribonucleasesFemaleHumansInterferonsPlacentaPregnancyVirus ReplicationZika VirusZika Virus InfectionConceptsZika virus infectionVirus infectionTrophoblast cellsPotential immune modulatory functionsInterferon-stimulated gene 20Anti-viral treatmentHigh-risk populationImmune modulatory functionsAnti-viral responseZika viral infectionImportance of preventionPregnant womenReplacement therapyViral infectionFetal developmentZika virusViral titersModulatory functionViral replicationInfectionAdverse effectsGene 20PregnancyPlacentaRNA virusesRestriction 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
Zika Virus Disrupts Phospho-TBK1 Localization and Mitosis in Human Neuroepithelial Stem Cells and Radial Glia
Onorati M, Li Z, Liu F, Sousa AMM, Nakagawa N, Li M, Dell’Anno M, Gulden FO, Pochareddy S, Tebbenkamp AT, Han W, Pletikos M, Gao T, Zhu Y, Bichsel C, Varela L, Szigeti-Buck K, Lisgo S, Zhang Y, Testen A, Gao XB, Mlakar J, Popovic M, Flamand M, Strittmatter SM, Kaczmarek LK, Anton ES, Horvath TL, Lindenbach BD, Sestan N. Zika Virus Disrupts Phospho-TBK1 Localization and Mitosis in Human Neuroepithelial Stem Cells and Radial Glia. Cell Reports 2016, 16: 2576-2592. PMID: 27568284, PMCID: PMC5135012, DOI: 10.1016/j.celrep.2016.08.038.Peer-Reviewed Original ResearchMeSH KeywordsAxl Receptor Tyrosine KinaseBrainCell DeathCentrosomeFetusGene Expression ProfilingHumansImmunity, InnateMicrocephalyMitochondriaMitosisNeocortexNeural Stem CellsNeuroepithelial CellsNeurogliaNeuronsNeuroprotective AgentsNucleosidesPhosphorylationProtein Kinase InhibitorsProtein Serine-Threonine KinasesProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesSpinal CordTranscription, GeneticVirus ReplicationZika VirusZika Virus InfectionConceptsRadial glial cellsNES cellsNeuroepithelial stem cellsZIKV infectionFetal brain slicesStem cellsEarly human neurodevelopmentHuman neuroepithelial stem cellsHuman neural stem cellsCell deathSingle-cell RNA-seqNeural stem cellsNeurodevelopment defectsZIKV replicationGlial cellsBrain slicesPotential treatmentRadial gliaZika virusPhospho-TBK1Neurodevelopmental defectsRNA-seqSupernumerary centrosomesNucleoside analoguesHuman neurodevelopmentVaginal Exposure to Zika Virus during Pregnancy Leads to Fetal Brain Infection
Yockey LJ, Varela L, Rakib T, Khoury-Hanold W, Fink SL, Stutz B, Szigeti-Buck K, Van den Pol A, Lindenbach BD, Horvath TL, Iwasaki A. Vaginal Exposure to Zika Virus during Pregnancy Leads to Fetal Brain Infection. Cell 2016, 166: 1247-1256.e4. PMID: 27565347, PMCID: PMC5006689, DOI: 10.1016/j.cell.2016.08.004.Peer-Reviewed Original ResearchMeSH KeywordsAbortion, HabitualAnimalsBrainBrain DiseasesDisease Models, AnimalFemaleFetal Growth RetardationInterferon Regulatory Factor-3MiceMice, Inbred C57BLMice, Mutant StrainsPregnancyPregnancy Complications, InfectiousReceptor, Interferon alpha-betaVaginaVirus ReplicationZika VirusZika Virus InfectionConceptsZika virusFetal brain infectionFetal growth restrictionLocal viral replicationWild-type miceType I interferon receptorZIKV challengeTranscription factor IRF3Vaginal exposureGenital mucosaBrain infectionWT miceEarly pregnancyZIKV infectionGrowth restrictionPregnant damsVaginal infectionsZIKV replicationFetal brainMouse modelIFN pathwayVaginal tractUnborn fetusViral replicationDisease consequencesThe 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 ResearchMeSH KeywordsGenome, ViralHepacivirusModels, MolecularNucleic Acid ConformationOpen Reading FramesRNA FoldingRNA, ViralVirus ReplicationConceptsRNA 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
2010
The 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
2006
Cell culture-grown hepatitis C virus is infectious in vivo and can be recultured in vitro
Lindenbach BD, Meuleman P, Ploss A, Vanwolleghem T, Syder AJ, McKeating JA, Lanford RE, Feinstone SM, Major ME, Leroux-Roels G, Rice CM. Cell culture-grown hepatitis C virus is infectious in vivo and can be recultured in vitro. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 3805-3809. PMID: 16484368, PMCID: PMC1533780, DOI: 10.1073/pnas.0511218103.Peer-Reviewed Original ResearchConceptsHepatitis C virusC virusCell culture-grown hepatitis C virusChronic liver diseaseHuman liver graftsHCV culture systemsHCV life cycleLong-term infectionLiver graftsLiver diseaseCurrent therapiesHepatocellular carcinomaCell culturesInfectious virusImproved infectivityMajor causeViral infectivityVivo cultureHCVccVirusInfectious cloneVivo dissectionInfectivityCulture systemCirrhosis
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 ResearchMeSH KeywordsAnimalsGene Expression Regulation, ViralGenome, ViralHepacivirusHumansRNA, ViralViral ProteinsVirus ReplicationComplete 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
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