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
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 inactivationVirusCellsPhenotypic properties of transmitted founder HIV-1
Parrish NF, Gao F, Li H, Giorgi EE, Barbian HJ, Parrish EH, Zajic L, Iyer SS, Decker JM, Kumar A, Hora B, Berg A, Cai F, Hopper J, Denny TN, Ding H, Ochsenbauer C, Kappes JC, Galimidi RP, West AP, Bjorkman PJ, Wilen CB, Doms RW, O’Brien M, Bhardwaj N, Borrow P, Haynes BF, Muldoon M, Theiler JP, Korber B, Shaw GM, Hahn BH. Phenotypic properties of transmitted founder HIV-1. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 6626-6633. PMID: 23542380, PMCID: PMC3637789, DOI: 10.1073/pnas.1304288110.Peer-Reviewed Original ResearchConceptsChemokine receptor 5TF virusesSubtype BT cellsFounder HIV-1Respective patient cohortsHIV-1 transmissionHIV-1 infectionDendritic cell interactionsT-cell tropismAIDS vaccine developmentPresence of IFNDe novo infectionIFN-α resistanceInfectious molecular cloneAIDS vaccinePatient cohortCell-free infectivityPrimary CD4HIV-1Env contentReceptor 5Virus-host interactionsNovo infectionVaccine development
2012
Transmitted/Founder and Chronic HIV-1 Envelope Proteins Are Distinguished by Differential Utilization of CCR5
Parker ZF, Iyer SS, Wilen CB, Parrish NF, Chikere KC, Lee FH, Didigu CA, Berro R, Klasse PJ, Lee B, Moore JP, Shaw GM, Hahn BH, Doms RW. Transmitted/Founder and Chronic HIV-1 Envelope Proteins Are Distinguished by Differential Utilization of CCR5. Journal Of Virology 2012, 87: 2401-2411. PMID: 23269796, PMCID: PMC3571396, DOI: 10.1128/jvi.02964-12.Peer-Reviewed Original ResearchConceptsCCR5 expression levelsF EnvsTransmitted/FounderHIV-1 envelope proteinCCR5 antagonist maravirocSingle genome amplificationExpression levelsSingle virus variantReplication-competent virusMVC resistanceFounder virusesChronic infectionCCR5 antagonistsT cellsHIV-1CCR5MaravirocControl virusPhysiologic levelsCCR5 conformationsVirus variantsEnvelope glycoproteinEnv proteinEnvInfection
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
2010
A Maraviroc-Resistant HIV-1 with Narrow Cross-Resistance to Other CCR5 Antagonists Depends on both N-Terminal and Extracellular Loop Domains of Drug-Bound CCR5
Tilton JC, Wilen CB, Didigu CA, Sinha R, Harrison JE, Agrawal-Gamse C, Henning EA, Bushman FD, Martin JN, Deeks SG, Doms RW. A Maraviroc-Resistant HIV-1 with Narrow Cross-Resistance to Other CCR5 Antagonists Depends on both N-Terminal and Extracellular Loop Domains of Drug-Bound CCR5. Journal Of Virology 2010, 84: 10863-10876. PMID: 20702642, PMCID: PMC2950574, DOI: 10.1128/jvi.01109-10.Peer-Reviewed Original ResearchMeSH KeywordsBase SequenceBinding SitesCCR5 Receptor AntagonistsCell LineCohort StudiesCyclohexanesDNA PrimersDrug Resistance, ViralHIV Envelope Protein gp120HIV Fusion InhibitorsHIV InfectionsHIV-1HumansIn Vitro TechniquesMaravirocModels, BiologicalMutant ProteinsMutationPeptide FragmentsProtein Structure, TertiaryReceptors, CCR5TriazolesConceptsCCR5 antagonistsLow CCR5 levelsTreatment-experienced patientsPlasma viral RNACCR5 antagonist maravirocCourse of treatmentHigh-level resistanceMVC resistanceMVC treatmentVirologic failureExtracellular loopCCR5 levelsTreatment regimensCross-resistance profilesCXCR4 useV3 loopCCR5 useHIV entryHIV-1Viral envelope proteinsCCR5V4 loopsAntagonistMaravirocPatients