2024
Electron tomography visualization of HIV-1 virions trapped by fusion inhibitors to host cells in infected tissues.
Ladinsky M, Zhu L, Ullah I, Uchil P, Kumar P, Kay M, Bjorkman P. Electron tomography visualization of HIV-1 virions trapped by fusion inhibitors to host cells in infected tissues. Journal Of Virology 2024, e0143224. PMID: 39475277, DOI: 10.1128/jvi.01432-24.Peer-Reviewed Original ResearchHIV-1 virionsHIV-1 target cellsHIV-1Fusion inhibitorsTarget cellsBone marrow/liver/thymus miceHIV-1 pseudovirionsCo-receptorHost cell membraneTZM-bl cellsPre-hairpin intermediateVascular endothelial cellsCell surfaceHumanized miceTZM-blCell membraneInfected tissuesEnvEndothelial cellsViral envelopeBind host receptorsHost receptorsInhibitorsCo-receptor proteinsPresence of virions
2022
HIV-1 Vpu restricts Fc-mediated effector functions in vivo
Prévost J, Anand S, Rajashekar J, Zhu L, Richard J, Goyette G, Medjahed H, Gendron-Lepage G, Chen H, Chen Y, Horwitz J, Grunst M, Zolla-Pazner S, Haynes B, Burton D, Flavell R, Kirchhoff F, Hahn B, Smith A, Pazgier M, Nussenzweig M, Kumar P, Finzi A. HIV-1 Vpu restricts Fc-mediated effector functions in vivo. Cell Reports 2022, 41: 111624. PMID: 36351384, PMCID: PMC9703018, DOI: 10.1016/j.celrep.2022.111624.Peer-Reviewed Original ResearchConceptsAntibody-dependent cellular cytotoxicityEffector functionsFc-mediated effector functionsHIV-1-infected cellsWild-type virusCorrelates of protectionRV144 vaccine trialHIV-1 infectionNon-neutralizing antibodiesFc effector functionsCell surface CD4Viral envelope glycoproteinsViral loadHumanized miceHumoral responseVaccine trialsCellular cytotoxicityHIV-1 VpuVpu expressionEnvelope glycoproteinInfected cellsNnAbsVirusVpuAdministration
2021
Long‐acting and extended‐release implant and nanoformulations with a synergistic antiretroviral two‐drug combination controls HIV‐1 infection in a humanized mouse model
Beloor J, Kudalkar SN, Buzzelli G, Yang F, Mandl HK, Rajashekar JK, Spasov KA, Jorgensen WL, Saltzman WM, Anderson KS, Kumar P. Long‐acting and extended‐release implant and nanoformulations with a synergistic antiretroviral two‐drug combination controls HIV‐1 infection in a humanized mouse model. Bioengineering & Translational Medicine 2021, 7: e10237. PMID: 35079625, PMCID: PMC8780078, DOI: 10.1002/btm2.10237.Peer-Reviewed Original ResearchNucleoside reverse transcriptase inhibitorHIV-1 infectionAntiretroviral therapyHIV-1-infected humanized miceTwo-drug combinationsHumanized mouse modelLong-term treatmentReverse transcriptase inhibitorMaintenance of CD4Nonnucleoside reverseHumanized miceAntiretroviral formulationsAdherence issuesARV combinationsTranscriptase inhibitorHIV pandemicT cellsMouse modelInjectable nanoformulationsTherapeutic indexNew drugsSustained levelsInfectionDrugsInterventionModulating HIV-1 envelope glycoprotein conformation to decrease the HIV-1 reservoir
Rajashekar JK, Richard J, Beloor J, Prévost J, Anand SP, Beaudoin-Bussières G, Shan L, Herndler-Brandstetter D, Gendron-Lepage G, Medjahed H, Bourassa C, Gaudette F, Ullah I, Symmes K, Peric A, Lindemuth E, Bibollet-Ruche F, Park J, Chen HC, Kaufmann DE, Hahn BH, Sodroski J, Pazgier M, Flavell RA, Smith AB, Finzi A, Kumar P. Modulating HIV-1 envelope glycoprotein conformation to decrease the HIV-1 reservoir. Cell Host & Microbe 2021, 29: 904-916.e6. PMID: 34019804, PMCID: PMC8214472, DOI: 10.1016/j.chom.2021.04.014.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, NeutralizingAntibody-Dependent Cell CytotoxicityAntiviral AgentsCD4 AntigensCD4-Positive T-LymphocytesCell LineEnv Gene Products, Human Immunodeficiency VirusEpitopesFemaleGlycoproteinsHEK293 CellsHIV InfectionsHIV-1HumansImmunoglobulin Fc FragmentsKiller Cells, NaturalMaleMiceMice, SCIDModels, AnimalProtein ConformationVirus ReplicationConceptsAntibody-dependent cellular cytotoxicityHIV-1 reservoirFc effector functionsViral reboundHumanized miceHIV-1HIV-1-infected individualsHIV-1-infected cellsAutologous HIV-1Natural killer cellsCD4-mimetic compoundsHIV-1 replicationSmall CD4-mimetic compoundsART interruptionFunctional cureNK cellsKiller cellsCellular cytotoxicityTherapeutic utilityInfected individualsCD4mcVirus reservoirMiceViral envelopeAntibody recognition
2019
Longitudinal bioluminescent imaging of HIV-1 infection during antiretroviral therapy and treatment interruption in humanized mice
Ventura JD, Beloor J, Allen E, Zhang T, Haugh KA, Uchil PD, Ochsenbauer C, Kieffer C, Kumar P, Hope TJ, Mothes W. Longitudinal bioluminescent imaging of HIV-1 infection during antiretroviral therapy and treatment interruption in humanized mice. PLOS Pathogens 2019, 15: e1008161. PMID: 31805155, PMCID: PMC6917343, DOI: 10.1371/journal.ppat.1008161.Peer-Reviewed Original ResearchConceptsHIV-1 infectionHumanized miceCombination antiretroviral therapy regimenViral spreadHIV-1 infection dynamicsNon-invasive bioluminescentAntiretroviral therapy regimenHIV-1 reporterSame lymphoid tissuesInfected cell populationCART withdrawalInfection recrudescenceAntiretroviral therapyTreatment interruptionTherapy regimenLymphoid tissueInfection dynamicsART treatmentBioluminescent imagingInfectionViral infection dynamicsInfected cellsCell populationsMiceBioluminescent signal
2016
Improvements and Limitations of Humanized Mouse Models for HIV Research: NIH/NIAID “Meet the Experts” 2015 Workshop Summary
Akkina R, Allam A, Balazs AB, Blankson JN, Burnett JC, Casares S, Garcia JV, Hasenkrug KJ, Kashanchi F, Kitchen SG, Klein F, Kumar P, Luster AD, Poluektova LY, Rao M, Sanders-Beer BE, Shultz LD, Zack JA. Improvements and Limitations of Humanized Mouse Models for HIV Research: NIH/NIAID “Meet the Experts” 2015 Workshop Summary. AIDS Research And Human Retroviruses 2016, 32: 109-119. PMID: 26670361, PMCID: PMC4761823, DOI: 10.1089/aid.2015.0258.Peer-Reviewed Original ResearchConceptsHuman leukocyte antigenHumanized mouse modelHuman immunodeficiency virusMouse modelCell engraftmentHuman hematopoietic cell engraftmentNIH/NIAIDHIV immune responsesImmunodeficient mouse strainsHematopoietic cell engraftmentHuman T cellsHIV reservoirXenogeneic graftImmunodeficiency syndromeHumanized miceImmunodeficiency virusLymphoid structuresLeukocyte antigenNew imaging techniquesT cellsImmune responseImmunodeficient miceHost responseHIV researchInfectious diseases
2015
Adenovirus-Vectored Broadly Neutralizing Antibodies Directed Against gp120 Prevent Human Immunodeficiency Virus Type 1 Acquisition in Humanized Mice
Liu S, Jackson A, Beloor J, Kumar P, Sutton RE. Adenovirus-Vectored Broadly Neutralizing Antibodies Directed Against gp120 Prevent Human Immunodeficiency Virus Type 1 Acquisition in Humanized Mice. Human Gene Therapy 2015, 26: 622-634. PMID: 25953321, PMCID: PMC4575530, DOI: 10.1089/hum.2014.146.Peer-Reviewed Original ResearchConceptsHumanized miceHuman immunodeficiency virus type 1 (HIV-1) acquisitionHuman immunodeficiency virus type 1Immunodeficiency virus type 1Plasma viral loadHigher serum levelsSingle intramuscular injectionBroadly Neutralizing AntibodiesVirus type 1First-generation adenoviral vectorsSerum levelsViral loadNeutralizing antibodiesIntramuscular injectionEffective vaccineT cellsHIV-1Therapeutic approachesHigh doseTherapeutic useType 1Adenoviral vectorAdV vectorsMiceAntibodies
2013
Site-specific Genome Editing in PBMCs With PLGA Nanoparticle-delivered PNAs Confers HIV-1 Resistance in Humanized Mice
Schleifman EB, McNeer NA, Jackson A, Yamtich J, Brehm MA, Shultz LD, Greiner DL, Kumar P, Saltzman WM, Glazer PM. Site-specific Genome Editing in PBMCs With PLGA Nanoparticle-delivered PNAs Confers HIV-1 Resistance in Humanized Mice. Molecular Therapy - Nucleic Acids 2013, 2: e135. PMID: 24253260, PMCID: PMC3889188, DOI: 10.1038/mtna.2013.59.Peer-Reviewed Original ResearchPeripheral blood mononuclear cellsHuman peripheral blood mononuclear cellsHIV-1 resistanceHumanized miceCCR5 geneMolecular Therapy-Nucleic Acids (2013) 2Plasma viral RNA loadNOD-scid ILR5-tropic strainsBlood mononuclear cellsViral RNA loadWeeks posttransplantationControl miceMononuclear cellsRNA loadT cellsHIV-1Biodegradable poly (lactide-co-glycolide) (PLGA) nanoparticlesCCR2 geneSingle treatmentMiceCCR5PLGA NPsPeptide nucleic acidPLGA nanoparticles
2008
T Cell-Specific siRNA Delivery Suppresses HIV-1 Infection in Humanized Mice
Kumar P, Ban HS, Kim SS, Wu H, Pearson T, Greiner DL, Laouar A, Yao J, Haridas V, Habiro K, Yang YG, Jeong JH, Lee KY, Kim YH, Kim SW, Peipp M, Fey GH, Manjunath N, Shultz LD, Lee SK, Shankar P. T Cell-Specific siRNA Delivery Suppresses HIV-1 Infection in Humanized Mice. Cell 2008, 134: 577-586. PMID: 18691745, PMCID: PMC2943428, DOI: 10.1016/j.cell.2008.06.034.Peer-Reviewed Original ResearchConceptsHIV infectionAntiviral siRNAsT cellsAnimal modelsCD4 T-cell countCD4 T-cell lossPeripheral blood mononuclear cellsSuppress HIV-1 infectionHu-HSC miceHu-PBL miceT-cell countsT cell lossHIV-1 infectionBlood mononuclear cellsNaive T cellsPreclinical animal modelsSuitable animal modelHumanized miceInfected miceMononuclear cellsSuppress viremiaCell countCell lossTherapeutic potentialHematopoietic stem cells