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
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 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
2018
Interaction between smoking and ATG16L1T300A triggers Paneth cell defects in Crohn's disease
Liu TC, Kern JT, VanDussen KL, Xiong S, Kaiko GE, Wilen CB, Rajala MW, Caruso R, Holtzman MJ, Gao F, McGovern DP, Nunez G, Head RD, Stappenbeck TS. Interaction between smoking and ATG16L1T300A triggers Paneth cell defects in Crohn's disease. Journal Of Clinical Investigation 2018, 128: 5110-5122. PMID: 30137026, PMCID: PMC6205411, DOI: 10.1172/jci120453.Peer-Reviewed Original ResearchConceptsPaneth cell defectsCD susceptibility genesSusceptibility genesCell defectsDisease-relevant phenotypesTranscriptional analysisCellular phenotypesApoptosis inhibitorCell-specific knockoutDisease subjectsFull-thickness ileumDistinct pathwaysCrohn's disease subjectsComplex inflammatory diseasePPARγ agonist rosiglitazoneCrypt base cellsEnvironmental risk factorsPaneth cellsGenesSelective downregulationCigarette smokingCrohn's diseasePhenotypeRelevant environmental exposuresCD subjects
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 NS1MNoV
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 phenotypeHomeostatic Control of Innate Lung Inflammation by Vici Syndrome Gene Epg5 and Additional Autophagy Genes Promotes Influenza Pathogenesis
Lu Q, Yokoyama CC, Williams JW, Baldridge MT, Jin X, DesRochers B, Bricker T, Wilen CB, Bagaitkar J, Loginicheva E, Sergushichev A, Kreamalmeyer D, Keller BC, Zhao Y, Kambal A, Green DR, Martinez J, Dinauer MC, Holtzman MJ, Crouch EC, Beatty W, Boon AC, Zhang H, Randolph GJ, Artyomov MN, Virgin HW. Homeostatic Control of Innate Lung Inflammation by Vici Syndrome Gene Epg5 and Additional Autophagy Genes Promotes Influenza Pathogenesis. Cell Host & Microbe 2016, 19: 102-113. PMID: 26764600, PMCID: PMC4714358, DOI: 10.1016/j.chom.2015.12.011.Peer-Reviewed Original ResearchConceptsAutophagy genesLung inflammationGene functionLethal influenza virus infectionBone marrow transplantation experimentsInnate immune inflammationInfluenza virus infectionEPG5Transplantation experimentsNormal homeostatic mechanismsHomeostatic controlInflammation supportLung transcriptomicsImmune inflammationRecurrent infectionsCytokine expressionInfluenza pathogenesisPulmonary abnormalitiesGenesInflammation resultsVirus infectionInfluenza resistanceElevated baselineHomeostatic mechanismsLung physiology