2022
Inflammasome activation in infected macrophages drives COVID-19 pathology
Sefik E, Qu R, Junqueira C, Kaffe E, Mirza H, Zhao J, Brewer JR, Han A, Steach HR, Israelow B, Blackburn HN, Velazquez SE, Chen YG, Halene S, Iwasaki A, Meffre E, Nussenzweig M, Lieberman J, Wilen CB, Kluger Y, Flavell RA. Inflammasome activation in infected macrophages drives COVID-19 pathology. Nature 2022, 606: 585-593. PMID: 35483404, PMCID: PMC9288243, DOI: 10.1038/s41586-022-04802-1.Peer-Reviewed Original ResearchConceptsInflammasome activationLung inflammationInflammatory responseInfected macrophagesSARS-CoV-2 infectionHuman macrophagesChronic lung pathologyPersistent lung inflammationSevere COVID-19Immune inflammatory responseInflammatory cytokine productionHumanized mouse modelNLRP3 inflammasome pathwayCOVID-19 pathologyCOVID-19SARS-CoV-2Productive viral cycleHyperinflammatory stateChronic stageIL-18Cytokine productionInflammatory cytokinesLung pathologyInflammasome pathwayInterleukin-1
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 ResearchConceptsIntercellular 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 cells
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
2016
Homeostatic 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
2011
Primary Infection by a Human Immunodeficiency Virus with Atypical Coreceptor Tropism
Jiang C, Parrish N, Wilen C, Li H, Chen Y, Pavlicek J, Berg A, Lu X, Song H, Tilton J, Pfaff J, Henning E, Decker J, Moody M, Drinker M, Schutte R, Freel S, Tomaras G, Nedellec R, Mosier D, Haynes B, Shaw G, Hahn B, Doms R, Gao F. Primary Infection by a Human Immunodeficiency Virus with Atypical Coreceptor Tropism. Journal Of Virology 2011, 85: 10669-10681. PMID: 21835785, PMCID: PMC3187499, DOI: 10.1128/jvi.05249-11.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsAmino Acid SubstitutionApelin ReceptorsCD4-Positive T-LymphocytesCells, CulturedEnv Gene Products, Human Immunodeficiency VirusGene ExpressionHIV-1HumansMacrophagesReceptors, Formyl PeptideReceptors, G-Protein-CoupledReceptors, HIVReceptors, LipoxinReceptors, PeptideViral TropismConceptsF virusesHuman immunodeficiency virus type 1Immunodeficiency virus type 1Alternative coreceptor GPR15Sequential plasma samplesHuman immunodeficiency virusClade B virusesVirus type 1Cell linesPrimary human CD4Third variable loopEarly time pointsCoreceptor tropismFounder virusesMultiple CD4Immunodeficiency virusAlternative coreceptorsCCR5 coreceptorPrimary infectionB virusCXCR4 coreceptorFPRL-1T cellsHuman CD4Homozygous donors