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 ResearchMeSH KeywordsAnimalsCaliciviridae InfectionsHumansMiceMice, Inbred C57BLNorovirusTropismViral Tropism
2020
UFMylation inhibits the proinflammatory capacity of interferon-γ–activated macrophages
Balce DR, Wang YT, McAllaster MR, Dunlap BF, Orvedahl A, Hykes BL, Droit L, Handley SA, Wilen CB, Doench JG, Orchard RC, Stallings CL, Virgin HW. UFMylation inhibits the proinflammatory capacity of interferon-γ–activated macrophages. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 118: e2011763118. PMID: 33372156, PMCID: PMC7817147, DOI: 10.1073/pnas.2011763118.Peer-Reviewed Original ResearchConceptsGenome-wide CRISPR knockout screenCRISPR knockout screensEndoplasmic reticulum stress responseRegulation of responsesReticulum stress responseKnockout screensTranscriptional responseGenetic roadmapIFN-γ responsesTumor necrosis factorNegative regulatorMolecular linkUfmylation pathwayUnexpected roleStress responseMacrophage cell lineIFN-γ activationIntracellular pathogensProinflammatory capacityConjugation systemInfluenza infectionCellular immunityIFN-γ effectsNecrosis factorImmune responseIntercellular Mitochondria Transfer to Macrophages Regulates White Adipose Tissue Homeostasis and Is Impaired in Obesity
Brestoff JR, Wilen CB, Moley JR, Li Y, Zou W, Malvin NP, Rowen MN, Saunders BT, Ma H, Mack MR, Hykes BL, Balce DR, Orvedahl A, Williams JW, Rohatgi N, Wang X, McAllaster MR, Handley SA, Kim BS, Doench JG, Zinselmeyer BH, Diamond MS, Virgin HW, Gelman AE, Teitelbaum SL. Intercellular Mitochondria Transfer to Macrophages Regulates White Adipose Tissue Homeostasis and Is Impaired in Obesity. Cell Metabolism 2020, 33: 270-282.e8. PMID: 33278339, PMCID: PMC7858234, DOI: 10.1016/j.cmet.2020.11.008.Peer-Reviewed Original ResearchMeSH KeywordsAdipose Tissue, WhiteAnimalsHomeostasisMacrophagesMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicMitochondriaObesityConceptsIntercellular mitochondria transferMitochondria transferMitochondria uptakeMetabolic homeostasisGenome-wide CRISPRWhite adipose tissue homeostasisWAT macrophagesDistinct macrophage subpopulationsKnockout screensTissue homeostasisHeparan sulfateAdipose tissue homeostasisWhite adipose tissueGenes EXT1HomeostasisImmunometabolic crosstalkMitochondriaAdipocytesMyeloid cellsMacrophage subpopulationsCellsVivoRecent studiesMacrophagesCRISPRCD300LF 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 cellsMouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling
Israelow B, Song E, Mao T, Lu P, Meir A, Liu F, Alfajaro MM, Wei J, Dong H, Homer RJ, Ring A, Wilen CB, Iwasaki A. Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling. Journal Of Experimental Medicine 2020, 217: e20201241. PMID: 32750141, PMCID: PMC7401025, DOI: 10.1084/jem.20201241.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin-Converting Enzyme 2AnimalsBetacoronavirusCell Line, TumorCoronavirus InfectionsCOVID-19DependovirusDisease Models, AnimalFemaleHumansInflammationInterferon Type ILungMaleMiceMice, Inbred C57BLMice, TransgenicPandemicsParvoviridae InfectionsPeptidyl-Dipeptidase APneumonia, ViralSARS-CoV-2Signal TransductionVirus ReplicationConceptsSARS-CoV-2Type I interferonMouse modelI interferonRobust SARS-CoV-2 infectionSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2SARS-CoV-2 infectionRespiratory syndrome coronavirus 2SARS-CoV-2 replicationCOVID-19 patientsSyndrome coronavirus 2Patient-derived virusesSignificant fatality ratePathological findingsInflammatory rolePathological responseEnzyme 2Receptor angiotensinFatality rateVaccine developmentGenetic backgroundViral replicationCoronavirus diseaseMiceCD300lf 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.MNoVPathogenesisSelect autophagy genes maintain quiescence of tissue-resident macrophages and increase susceptibility to Listeria monocytogenes
Wang YT, Zaitsev K, Lu Q, Li S, Schaiff WT, Kim KW, Droit L, Wilen CB, Desai C, Balce DR, Orchard RC, Orvedahl A, Park S, Kreamalmeyer D, Handley SA, Pfeifer JD, Baldridge MT, Artyomov MN, Stallings CL, Virgin HW. Select autophagy genes maintain quiescence of tissue-resident macrophages and increase susceptibility to Listeria monocytogenes. Nature Microbiology 2020, 5: 272-281. PMID: 31959973, PMCID: PMC7147835, DOI: 10.1038/s41564-019-0633-0.Peer-Reviewed Original ResearchConceptsTissue-resident macrophagesAutophagy genesDegradative autophagyBeclin-1Maintenance of proteinMyeloid cells resultsAutophagy protein Beclin 1Protein Beclin 1Organelle integrityCellular processesMyeloid cellsBacterial microbiotaCytoplasmic contentsLysosomal digestionGenesCommensal microorganismsCells resultsAutophagyFIP200Homeostatic functionsListeria monocytogenes infectionAdaptive immune responsesKey functionsMice displayMacrophage response
2019
The intestinal regionalization of acute norovirus infection is regulated by the microbiota via bile acid-mediated priming of type III interferon
Grau KR, Zhu S, Peterson ST, Helm EW, Philip D, Phillips M, Hernandez A, Turula H, Frasse P, Graziano VR, Wilen CB, Wobus CE, Baldridge MT, Karst SM. The intestinal regionalization of acute norovirus infection is regulated by the microbiota via bile acid-mediated priming of type III interferon. Nature Microbiology 2019, 5: 84-92. PMID: 31768030, PMCID: PMC6925324, DOI: 10.1038/s41564-019-0602-7.Peer-Reviewed Original ResearchConceptsNorovirus infectionType III interferonsMurine norovirus infectionCommensal bacteriaIII interferonsIntestinal microbiotaType III interferon responseBile acid receptorProximal small intestineRegional expression profilesProximal gutAntibiotic treatmentViral infectionSmall intestineIntestinal tractAcid receptorsInfectionInterferon responseMicrobiotaInterferonPathogenic enteric virusesEnteric virusesHost metabolitesGutExpression profiles
2017
Norovirus Cell Tropism Is Determined by Combinatorial Action of a Viral Non-structural Protein and Host Cytokine
Lee S, Wilen CB, Orvedahl A, McCune BT, Kim KW, Orchard RC, Peterson ST, Nice TJ, Baldridge MT, Virgin HW. Norovirus Cell Tropism Is Determined by Combinatorial Action of a Viral Non-structural Protein and Host Cytokine. Cell Host & Microbe 2017, 22: 449-459.e4. PMID: 28966054, PMCID: PMC5679710, DOI: 10.1016/j.chom.2017.08.021.Peer-Reviewed Original ResearchConceptsIntestinal epithelial cellsViral surface proteinsCellular tropismPersistent viral infectionNon-structural protein NS1Expression of NS1MNoV infectionSurface proteinsHost cytokinesAntiviral immunityHost determinantsInterferon lambdaViral infectionKey host determinantsViral non-structural proteinsCell tropismFecal sheddingNon-structural proteinsTropism determinantsEpithelial cellsGlobal causeInfectionTropismProtein NS1MNoVViral 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
2016
CD4 Receptor is a Key Determinant of Divergent HIV-1 Sensing by Plasmacytoid Dendritic Cells
O’Brien M, Manches O, Wilen C, Gopal R, Huq R, Wu V, Sunseri N, Bhardwaj N. CD4 Receptor is a Key Determinant of Divergent HIV-1 Sensing by Plasmacytoid Dendritic Cells. PLOS Pathogens 2016, 12: e1005553. PMID: 27082754, PMCID: PMC4833349, DOI: 10.1371/journal.ppat.1005553.Peer-Reviewed Original ResearchConceptsPlasmacytoid dendritic cellsAntigen presenting cellsI interferonDendritic cellsNF-κBMature dendritic cell phenotypePotent antigen presenting cellsToll-like receptor 7/9HIV-1 sensingDendritic cell phenotypeInnate immune cellsNF-κB pathwayType I interferonViral nucleic acidsIRF7 pathwayPDC activationImmune cellsPresenting cellsDisease progressionHIV virionsHIV-1IFN productionCD4 receptorInadequate maturationCell phenotype