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 virionsCD4 downregulation precedes Env expression and protects HIV-1-infected cells from ADCC mediated by non-neutralizing antibodies
Richard J, Sannier G, Zhu L, Prévost J, Marchitto L, Benlarbi M, Beaudoin-Bussières G, Kim H, Sun Y, Chatterjee D, Medjahed H, Bourassa C, Delgado G, Dubé M, Kirchhoff F, Hahn B, Kumar P, Kaufmann D, Finzi A. CD4 downregulation precedes Env expression and protects HIV-1-infected cells from ADCC mediated by non-neutralizing antibodies. MBio 2024, 15: e01827-24. PMID: 39373535, PMCID: PMC11559134, DOI: 10.1128/mbio.01827-24.Peer-Reviewed Original ResearchAntibody-dependent cellular cytotoxicityProductively infected cellsEnv-CD4 interactionNon-neutralizing antibodiesHIV-1CD4 downmodulationEnv expressionCellular cytotoxicityResistance to antibody-dependent cellular cytotoxicityHIV-1-infected humanized miceInfected cellsHIV-1 cure strategiesHIV-1 mRNA expressionHIV-1-infected cellsCD4+ T cellsHIV-1 envelope glycoproteinMRNA expressionADCC-mediating antibodiesNon-neutralizing AbsCell surface CD4HIV-1 isolatesImmunotherapy-based strategiesMultiparametric flow cytometryVirally infected cellsEffective immune response
2023
HIV-1 Remission: Accelerating the Path to Permanent HIV-1 Silencing
Lyons D, Kumar P, Roan N, Defechereux P, Feschotte C, Lange U, Murthy N, Sameshima P, Verdin E, Ake J, Parsons M, Nath A, Gianella S, Smith D, Kallas E, Villa T, Strange R, Mwesigwa B, O’Brien R, Nixon D, Ndhlovu L, Valente S, Ott M. HIV-1 Remission: Accelerating the Path to Permanent HIV-1 Silencing. Viruses 2023, 15: 2171. PMID: 38005849, PMCID: PMC10674359, DOI: 10.3390/v15112171.Peer-Reviewed Original Research
2021
Modulating 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
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 vectorsMiceAntibodiesBroad CTL response is required to clear latent HIV-1 due to dominance of escape mutations
Deng K, Pertea M, Rongvaux A, Wang L, Durand CM, Ghiaur G, Lai J, McHugh HL, Hao H, Zhang H, Margolick JB, Gurer C, Murphy AJ, Valenzuela DM, Yancopoulos GD, Deeks SG, Strowig T, Kumar P, Siliciano JD, Salzberg SL, Flavell RA, Shan L, Siliciano RF. Broad CTL response is required to clear latent HIV-1 due to dominance of escape mutations. Nature 2015, 517: 381-385. PMID: 25561180, PMCID: PMC4406054, DOI: 10.1038/nature14053.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAnimalsAnti-HIV AgentsCD4-Positive T-LymphocytesChronic DiseaseEpitopes, T-LymphocyteFemaleGag Gene Products, Human Immunodeficiency VirusGenes, DominantGenes, ViralHIV InfectionsHIV-1HumansMaleMiceMutationRNA, ViralT-Lymphocytes, CytotoxicViral LoadVirus LatencyVirus Replication
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