2023
IFN-λ derived from nonsusceptible enterocytes acts on tuft cells to limit persistent norovirus
Ingle H, Makimaa H, Aggarwal S, Deng H, Foster L, Li Y, Kennedy E, Peterson S, Wilen C, Lee S, Suthar M, Baldridge M. IFN-λ derived from nonsusceptible enterocytes acts on tuft cells to limit persistent norovirus. Science Advances 2023, 9: eadi2562. PMID: 37703370, PMCID: PMC10499323, DOI: 10.1126/sciadv.adi2562.Peer-Reviewed Original ResearchConceptsIntestinal epithelial cellsTuft cellsUninfected bystander cellsIFN-λ signalingSource of IFNImmune cellsIntestinal infectionsLeading causeViral gastroenteritisMNoVNorovirus pathogenesisCellular tropismPotent antiviralEpidemic viral gastroenteritisEpithelial cellsBystander cellsIFNNorovirusAntiviralsInfectionMurine norovirusIntercellular communicationPersistent strainsCellsVivoMurine Norovirus: Additional Protocols for Basic and Antiviral Studies
Wobus C, Peiper A, McSweeney A, Young V, Chaika M, Lane M, Lingemann M, Deerain J, Strine M, Alfajaro M, Helm E, Karst S, Mackenzie J, Taube S, Ward V, Wilen C. Murine Norovirus: Additional Protocols for Basic and Antiviral Studies. Current Protocols 2023, 3: e828. PMID: 37478303, PMCID: PMC10375541, DOI: 10.1002/cpz1.828.Peer-Reviewed Original Research
2022
Tuft-cell-intrinsic and -extrinsic mediators of norovirus tropism regulate viral immunity
Strine M, Alfajaro M, Graziano V, Song J, Hsieh L, Hill R, Guo J, VanDussen K, Orchard R, Baldridge M, Lee S, Wilen C. Tuft-cell-intrinsic and -extrinsic mediators of norovirus tropism regulate viral immunity. Cell Reports 2022, 41: 111593. PMID: 36351394, PMCID: PMC9662704, DOI: 10.1016/j.celrep.2022.111593.Peer-Reviewed Original ResearchTuft cells are key mediators of interkingdom interactions at mucosal barrier surfaces
Strine MS, Wilen CB. Tuft cells are key mediators of interkingdom interactions at mucosal barrier surfaces. PLOS Pathogens 2022, 18: e1010318. PMID: 35271673, PMCID: PMC8912186, DOI: 10.1371/journal.ppat.1010318.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsInterkingdom interactionsTuft cellsCell biologyImmune responseMicrobial activationMicrobial sensingCell abundanceMucosal barrier surfacesAntiviral adaptive immune responsesType 2 immune responsesCell heterogeneityExquisite specificityMucosal barrier integrityAdaptive immune responsesMurine norovirusHuman healthKey orchestratorsMicrobial infectionsPathogenic bacteriaBroad intraFlavivirus replicationKey mediatorContext of coinfectionTissue repairImmune evasion
2021
CD300lf Conditional Knockout Mouse Reveals Strain-Specific Cellular Tropism of Murine Norovirus
Graziano VR, Alfajaro MM, Schmitz CO, Filler RB, Strine MS, Wei J, Hsieh LL, Baldridge MT, Nice TJ, Lee S, Orchard RC, Wilen CB. CD300lf Conditional Knockout Mouse Reveals Strain-Specific Cellular Tropism of Murine Norovirus. Journal Of Virology 2021, 95: 10.1128/jvi.01652-20. PMID: 33177207, PMCID: PMC7925115, DOI: 10.1128/jvi.01652-20.Peer-Reviewed Original ResearchConceptsConditional knockout miceIntestinal epithelial cellsCell tropismKnockout miceTuft cellsDendritic cellsMyelomonocytic cellsB cellsCellular tropismMurine norovirusEpithelial cellsViral RNA levelsInnate immune responseCause of gastroenteritisMNoV infectionCell typesViral loadGastrointestinal infectionsReceptor expressionImmunocompetent humansImmune responseCell type-specific rolesMouse modelIntestinal tissueMNoV
2020
CD300LF Polymorphisms of Inbred Mouse Strains Confer Resistance to Murine Norovirus Infection in a Cell Type-Dependent Manner
Furlong K, Biering SB, Choi J, Wilen CB, Orchard RC, Wobus CE, Nelson CA, Fremont DH, Baldridge MT, Randall G, Hwang S. CD300LF Polymorphisms of Inbred Mouse Strains Confer Resistance to Murine Norovirus Infection in a Cell Type-Dependent Manner. Journal Of Virology 2020, 94: 10.1128/jvi.00837-20. PMID: 32581099, PMCID: PMC7431780, DOI: 10.1128/jvi.00837-20.Peer-Reviewed Original ResearchConceptsBone marrow-derived macrophagesCell type-dependent mannerType-dependent mannerCell typesMacrophage-like cellsRobust experimental systemMNV infectionRelated murine norovirusSpecific cell typesCorresponding mutantsMarrow-derived macrophagesMurine norovirus infectionEntry factorsMurine norovirusCD300lfCause of gastroenteritisNonpermissive cellsProteinaceous receptorsConfer resistanceHuman cellsHost cellsDifferent allelesAmino acidsC57BL/6J allelePermissive cellsCD300lf is the primary physiologic receptor of murine norovirus but not human norovirus
Graziano VR, Walker FC, Kennedy EA, Wei J, Ettayebi K, Strine MS, Filler RB, Hassan E, Hsieh LL, Kim AS, Kolawole AO, Wobus CE, Lindesmith LC, Baric RS, Estes MK, Orchard RC, Baldridge MT, Wilen CB. CD300lf is the primary physiologic receptor of murine norovirus but not human norovirus. PLOS Pathogens 2020, 16: e1008242. PMID: 32251490, PMCID: PMC7162533, DOI: 10.1371/journal.ppat.1008242.Peer-Reviewed Original ResearchConceptsMNoV infectionPrimary physiologic receptorPhysiologic receptorHuman norovirusMurine norovirusBona fide receptorHumoral responseVirus infectionEntry receptorReceptor utilizationCell tropismInfectionReceptorsVirus-like particlesFide receptorCD300lfNorovirusHNoVCD300ldMajor determinantProteinaceous receptorsVivoMNoV.MNoVPathogenesis
2019
Norovirus Attachment and Entry
Graziano VR, Wei J, Wilen CB. Norovirus Attachment and Entry. Viruses 2019, 11: 495. PMID: 31151248, PMCID: PMC6630345, DOI: 10.3390/v11060495.Peer-Reviewed Original ResearchConceptsHisto-blood group antigensNorovirus attachmentMajority of casesMajor human pathogenViral life cycleImmune interactionsViral gastroenteritisCell tropismGroup antigensViral entryKey mediatorHuman norovirusBile saltsViral genome releaseMurine norovirusReceptorsMinor capsid protein VP2Capsid protein VP2Human pathogensMolecular mechanismsNorovirusSignificant determinantsProtein VP2Important future directionsCurrent understandingA Secreted Viral Nonstructural Protein Determines Intestinal Norovirus Pathogenesis
Lee S, Liu H, Wilen CB, Sychev ZE, Desai C, Hykes BL, Orchard RC, McCune BT, Kim KW, Nice TJ, Handley SA, Baldridge MT, Amarasinghe GK, Virgin HW. A Secreted Viral Nonstructural Protein Determines Intestinal Norovirus Pathogenesis. Cell Host & Microbe 2019, 25: 845-857.e5. PMID: 31130511, PMCID: PMC6622463, DOI: 10.1016/j.chom.2019.04.005.Peer-Reviewed Original ResearchConceptsNS1 secretionTuft cellsIFN-λ responseAnti-capsid antibodiesMNoV infectionAcute infectionIntestinal infectionsLack of inductionPersistent infectionNorovirus pathogenesisCaspase-3 cleavageIFN responseInfectionSecretionViral nonstructural proteinsIFNProtein 1/2Viral proteinsMurine norovirusNS1Lower percentageNonstructural proteinsCellsLow numberVaccination
2018
Sphingolipid biosynthesis induces a conformational change in the murine norovirus receptor and facilitates viral infection
Orchard RC, Wilen CB, Virgin HW. Sphingolipid biosynthesis induces a conformational change in the murine norovirus receptor and facilitates viral infection. Nature Microbiology 2018, 3: 1109-1114. PMID: 30127493, PMCID: PMC6158067, DOI: 10.1038/s41564-018-0221-8.Peer-Reviewed Original ResearchConceptsSerine palmitoyltransferase complexSphingolipid biosynthesisCellular susceptibilityConformational changesLipid biosynthetic enzymesDe novo sphingolipid biosynthesisHost cellular receptorsSerine palmitoyltransferase activityBiosynthetic enzymesBiosynthetic pathwayMurine norovirus infectionMurine norovirusCD300lfCell surfaceBiosynthesisUnappreciated connectionCellular receptorsExtracellular ceramideReceptor conformationViral infectionSurface expressionTarget cell surfaceViral bindingPalmitoyltransferase activityReceptors
2017
Viral Replication Complexes Are Targeted by LC3-Guided Interferon-Inducible GTPases
Biering SB, Choi J, Halstrom RA, Brown HM, Beatty WL, Lee S, McCune BT, Dominici E, Williams LE, Orchard RC, Wilen CB, Yamamoto M, Coers J, Taylor GA, Hwang S. Viral Replication Complexes Are Targeted by LC3-Guided Interferon-Inducible GTPases. Cell Host & Microbe 2017, 22: 74-85.e7. PMID: 28669671, PMCID: PMC5591033, DOI: 10.1016/j.chom.2017.06.005.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutophagyCaliciviridae InfectionsCarrier ProteinsCell LineCytosolFemaleFibroblastsGene Knockdown TechniquesGTP PhosphohydrolasesHeLa CellsHumansImmunity, InnateInterferon-gammaInterferonsMacrophagesMaleMiceMice, Inbred C57BLMicrotubule-Associated ProteinsNorovirusRAW 264.7 CellsVacuolesViral Plaque AssayVirus ReplicationConceptsViral replication complexReplication complexImmunity-related GTPasesGuanylate-binding proteinsIFN-inducible GTPasesMNV replication complexPositive-sense RNA genomeLC3 conjugation systemConjugation systemInterferon-inducible GTPasesMembranes of vacuolesAutophagy proteinsRNA genomeGTPasesDiverse pathogensMNV replicationHuman cellsAdvantageous microenvironmentImmune defense mechanismsMembranous structuresDefense mechanismsMurine norovirusHost immune systemMembrane structureProtein