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
2013
Simultaneous zinc-finger nuclease editing of the HIV coreceptors ccr5 and cxcr4 protects CD4+ T cells from HIV-1 infection
Didigu CA, Wilen CB, Wang J, Duong J, Secreto AJ, Danet-Desnoyers GA, Riley JL, Gregory PD, June CH, Holmes MC, Doms RW. Simultaneous zinc-finger nuclease editing of the HIV coreceptors ccr5 and cxcr4 protects CD4+ T cells from HIV-1 infection. Blood 2013, 123: 61-69. PMID: 24162716, PMCID: PMC3879906, DOI: 10.1182/blood-2013-08-521229.Peer-Reviewed Original ResearchConceptsC chemokine receptor 5HIV-1 infectionT cellsHIV-1HIV coreceptor CCR5Chemokine receptor 5Humanized mouse modelDrug-free treatmentHIV-1 entryHIV coreceptorsPharmacologic blockadeCoreceptor CCR5Mouse modelCells engraftReceptor 5Gene-modified cellsCXCR4InfectionPrimary humanCoreceptorCD4CCR5Genetic inactivationVirusCells
2011
Engineering HIV-Resistant Human CD4+ T Cells with CXCR4-Specific Zinc-Finger Nucleases
Wilen CB, Wang J, Tilton JC, Miller JC, Kim KA, Rebar EJ, Sherrill-Mix SA, Patro SC, Secreto AJ, Jordan AP, Lee G, Kahn J, Aye PP, Bunnell BA, Lackner AA, Hoxie JA, Danet-Desnoyers GA, Bushman FD, Riley JL, Gregory PD, June CH, Holmes MC, Doms RW. Engineering HIV-Resistant Human CD4+ T Cells with CXCR4-Specific Zinc-Finger Nucleases. PLOS Pathogens 2011, 7: e1002020. PMID: 21533216, PMCID: PMC3077364, DOI: 10.1371/journal.ppat.1002020.Peer-Reviewed Original ResearchConceptsT cellsHIV-1Human CD4X4-tropic HIV-1X4 HIV-1CCR5-tropic virusHumanized mouse modelLoss of CXCR4CXCR4-tropic HIVHIV-1 entryHuman T cellsCCR5Δ32 polymorphismAdoptive transferAutologous transplantCell surface expressionCXCR4 coreceptorMouse modelCD4CCR5CXCR4Surface expressionHIVInfectionSuch cellsHost cells