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
Bile Salts Alter the Mouse Norovirus Capsid Conformation: Possible Implications for Cell Attachment and Immune Evasion
Sherman MB, Williams AN, Smith HQ, Nelson C, Wilen CB, Fremont DH, Virgin HW, Smith TJ. Bile Salts Alter the Mouse Norovirus Capsid Conformation: Possible Implications for Cell Attachment and Immune Evasion. Journal Of Virology 2019, 93: 10.1128/jvi.00970-19. PMID: 31341042, PMCID: PMC6744230, DOI: 10.1128/jvi.00970-19.Peer-Reviewed Original ResearchConceptsCryo-EM structureP domainCryo-electron microscopy structureHigh-resolution cryo-EM structuresConformational changesImportant biological rolesSmall conformational changesMicroscopy structureHuman Norwalk virusCell attachmentAdjacent subunitsBiological roleIcosahedral capsidCapsid shellRNA virusesCapsid proteinBinding sitesIntrinsic affinityReceptor binding sitesCapsid conformationUnusual structureImmune evasionShell domainTarget cellsReceptorsNorovirus 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 understanding
2018
Structural basis for murine norovirus engagement of bile acids and the CD300lf receptor
Nelson CA, Wilen CB, Dai YN, Orchard RC, Kim AS, Stegeman RA, Hsieh LL, Smith TJ, Virgin HW, Fremont DH. Structural basis for murine norovirus engagement of bile acids and the CD300lf receptor. Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 115: e9201-e9210. PMID: 30194229, PMCID: PMC6166816, DOI: 10.1073/pnas.1805797115.Peer-Reviewed Original ResearchConceptsP domainCognate cellular receptorDomain dimer interfaceDimer interfaceBiophysical assaysStructural basisCD300lfResidue mutationsP2 subdomainAcid bindingCell surfaceHost ligandsCellular receptorsProtruding (P) domainStructural determinantsDE loopMonomeric affinityBinding sitesX-ray crystal structurePotential modulatorsReceptor binding sitesMNoVCrystal structureDivalent cationsReceptorsSphingolipid 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 activityReceptorsTropism for tuft cells determines immune promotion of norovirus pathogenesis
Wilen CB, Lee S, Hsieh LL, Orchard RC, Desai C, Hykes BL, McAllaster MR, Balce DR, Feehley T, Brestoff JR, Hickey CA, Yokoyama CC, Wang YT, MacDuff DA, Kreamalmayer D, Howitt MR, Neil JA, Cadwell K, Allen PM, Handley SA, van Lookeren Campagne M, Baldridge MT, Virgin HW. Tropism for tuft cells determines immune promotion of norovirus pathogenesis. Science 2018, 360: 204-208. PMID: 29650672, PMCID: PMC6039974, DOI: 10.1126/science.aar3799.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCaliciviridae InfectionsCell ProliferationCytokinesEnterocytesMiceMicrobiotaNorovirusReceptors, ImmunologicViral TropismConceptsVirus infectionImmune promotionTuft cellsType 2 cytokinesEnteric virus infectionEnteric viral infectionsIntestinal epithelial cellsMNoV infectionNorovirus infectionCommensal microbiotaHost immunityViral infectionNorovirus pathogenesisRare typeImmune systemCellular tropismInfectionMouse intestineTarget cellsEpithelial cellsCell proliferationCytokinesTropismCD300lfCells
2016
Discovery of a proteinaceous cellular receptor for a norovirus
Orchard RC, Wilen CB, Doench JG, Baldridge MT, McCune BT, Lee YC, Lee S, Pruett-Miller SM, Nelson CA, Fremont DH, Virgin HW. Discovery of a proteinaceous cellular receptor for a norovirus. Science 2016, 353: 933-936. PMID: 27540007, PMCID: PMC5484048, DOI: 10.1126/science.aaf1220.Peer-Reviewed Original ResearchConceptsProteinaceous receptorsMNoV infectionCellular machineryNoV replicationHuman cellsCell deathSpecies barrierCD300lfSpecies tropismPrimary cellsCellular receptorsCell linesMurine NoVHost factorsReplicationCause of gastroenteritisPrimary determinantNoV infectionReceptorsCellsEctodomainMachineryInfectionCrystal structureResidues