2022
Coronavirus Lung Infection Impairs Host Immunity against Secondary Bacterial Infection by Promoting Lysosomal Dysfunction.
Peng X, Kim J, Gupta G, Agaronyan K, Mankowski MC, Korde A, Takyar SS, Shin HJ, Habet V, Voth S, Audia JP, Chang D, Liu X, Wang L, Cai Y, Tian X, Ishibe S, Kang MJ, Compton S, Wilen CB, Dela Cruz CS, Sharma L. Coronavirus Lung Infection Impairs Host Immunity against Secondary Bacterial Infection by Promoting Lysosomal Dysfunction. The Journal Of Immunology 2022, 209: 1314-1322. PMID: 36165196, PMCID: PMC9523490, DOI: 10.4049/jimmunol.2200198.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Bacterial infectionsMouse modelCoronavirus infectionLysosomal dysfunctionMajor health care challengeLung immune cellsLung tissue damageSecondary bacterial infectionImpair host immunityIL-1β releaseHealth care challengesCell deathPyroptotic cell deathBacterial killing abilityIL-1βBacterial clearanceImmune cellsSecondary infectionHost immunityAlveolar macrophagesTissue damageΒ-coronavirusStructural cellsCare challenges
2021
A stem-loop RNA RIG-I agonist protects against acute and chronic SARS-CoV-2 infection in mice
Mao T, Israelow B, Lucas C, Vogels CBF, Gomez-Calvo ML, Fedorova O, Breban MI, Menasche BL, Dong H, Linehan M, Alpert T, Anderson F, Earnest R, Fauver J, Kalinich C, Munyenyembe K, Ott I, Petrone M, Rothman J, Watkins A, Wilen C, Landry M, Grubaugh N, Pyle A, Iwasaki A. A stem-loop RNA RIG-I agonist protects against acute and chronic SARS-CoV-2 infection in mice. Journal Of Experimental Medicine 2021, 219: e20211818. PMID: 34757384, PMCID: PMC8590200, DOI: 10.1084/jem.20211818.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionChronic SARS-CoV-2 infectionVariants of concernLethal SARS-CoV-2 infectionPost-infection therapyLower respiratory tractPost-exposure treatmentType I interferonSARS-CoV-2Effective medical countermeasuresAdaptive immune systemBroad-spectrum antiviralsContext of infectionSingle doseRespiratory tractViral controlImmunodeficient miceSevere diseaseMouse modelI interferonViral infectionImmune systemInnate immunityDisease preventionConsiderable efficacyCD300lf 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
An ACE2 Microbody Containing a Single Immunoglobulin Fc Domain Is a Potent Inhibitor of SARS-CoV-2
Tada T, Fan C, Chen JS, Kaur R, Stapleford KA, Gristick H, Dcosta BM, Wilen CB, Nimigean CM, Landau NR. An ACE2 Microbody Containing a Single Immunoglobulin Fc Domain Is a Potent Inhibitor of SARS-CoV-2. Cell Reports 2020, 33: 108528. PMID: 33326798, PMCID: PMC7705358, DOI: 10.1016/j.celrep.2020.108528.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAngiotensin-Converting Enzyme 2AnimalsAntiviral AgentsCOVID-19Disease Models, AnimalDisulfidesFemaleHEK293 CellsHumansImmunoglobulin Fc FragmentsMaleMice, TransgenicMicrobodiesProtein DomainsProtein MultimerizationSARS-CoV-2Spike Glycoprotein, CoronavirusVirionVirus InternalizationConceptsSARS-CoV-2Soluble ACE2Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionAcute respiratory syndrome coronavirus 2 infectionLive SARS-CoV-2Syndrome coronavirus 2 infectionCoronavirus 2 infectionSARS-CoV-2 spikeCoronavirus disease 2019SARS-CoV-2 spike proteinDisease 2019Enzyme 2Mouse modelFuture coronavirusesFc fusion proteinΒ-coronavirusViral variantsImmunoglobulin heavy chainSpike proteinACE2 ectodomainImmunoglobulin Fc domainFc domainVirusACE2Potent inhibitorMouse 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 diseaseMice
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