2023
The KDM6A-KMT2D-p300 axis regulates susceptibility to diverse coronaviruses by mediating viral receptor expression
Wei J, Alfajaro M, Cai W, Graziano V, Strine M, Filler R, Biering S, Sarnik S, Patel S, Menasche B, Compton S, Konermann S, Hsu P, Orchard R, Yan Q, Wilen C. The KDM6A-KMT2D-p300 axis regulates susceptibility to diverse coronaviruses by mediating viral receptor expression. PLOS Pathogens 2023, 19: e1011351. PMID: 37410700, PMCID: PMC10325096, DOI: 10.1371/journal.ppat.1011351.Peer-Reviewed Original ResearchConceptsMouse hepatitis virusReceptor expressionTherapeutic targetMERS-CoVMajor SARS-CoV-2 variantsPrimary human airwaySARS-CoV-2 variantsNovel therapeutic targetViral receptor expressionSARS-CoV-2Histone methyltransferase KMT2DIntestinal epithelial cellsCoronavirus SusceptibilityDiverse coronavirusesHistone demethylase KDM6ADPP4 expressionCoronavirus receptorsHost determinantsHepatitis virusHuman airwaysSARS-CoVSmall molecule inhibitionViral entryPotential drug targetsViral receptors
2020
Cytidine Monophosphate N-Acetylneuraminic Acid Synthetase and Solute Carrier Family 35 Member A1 Are Required for Reovirus Binding and Infection
Urbanek K, Sutherland DM, Orchard RC, Wilen CB, Knowlton JJ, Aravamudhan P, Taylor GM, Virgin HW, Dermody TS. Cytidine Monophosphate N-Acetylneuraminic Acid Synthetase and Solute Carrier Family 35 Member A1 Are Required for Reovirus Binding and Infection. Journal Of Virology 2020, 95: 10.1128/jvi.01571-20. PMID: 33087464, PMCID: PMC7944449, DOI: 10.1128/jvi.01571-20.Peer-Reviewed Original ResearchConceptsSialic acid expressionMicroglial cellsCell surface expressionReovirus-induced cell deathReovirus infectionSialic acidMurine microglial BV2 cellsReovirus-induced diseaseMember A1Microglial BV2 cellsSurface expressionMurine microglial cellsCell deathReovirus bindingBV2 cellsViral tropismInfectionHost genesLow-level bindingCell surface receptorsHost factorsCell surfaceReceptorsSialic acid synthesisSurface receptorsCD300LF 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
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