2025
Safety, pharmacokinetics, and biological activity of CD4-mimetic BNM-III-170 in SHIV-infected rhesus macaques
Viox E, Richard J, Grandea A, Nguyen K, Harper J, Auger J, Ding S, Gasser R, Prévost J, Marchitto L, Medjahed H, Bourassa C, Gaudette F, Pagliuzza A, Trifone C, Gavegnano C, Hurwitz S, Park J, Clark N, Hammad I, Capuano S, Martin M, Schinazi R, Silvestri G, Kulpa D, Kumar P, Chomont N, Pazgier M, Smith A, Sodroski J, Evans D, Finzi A, Paiardini M. Safety, pharmacokinetics, and biological activity of CD4-mimetic BNM-III-170 in SHIV-infected rhesus macaques. Journal Of Virology 2025, 99: e00062-25. PMID: 40192306, PMCID: PMC12090809, DOI: 10.1128/jvi.00062-25.Peer-Reviewed Original ResearchConceptsSHIV-infected rhesus macaquesShock-and-kill approachADCC-mediating antibodiesCD4-inducedHIV-1Rhesus macaquesDosing regimenSmall-molecule CD4-mimetic compoundsGp120 subunit of EnvLatent HIV-1 reservoirHIV-1 envelope glycoproteinAnti-HIV-1 antibodiesInfected cellsPlasma of treated animalsCD4-mimetic compoundsCure HIV-1HIV-1 reservoirUninfected rhesus macaquesPlasma viral loadBind to infected cellsHIV-1 EnvNon-neutralizing antibodiesCD4-bound conformationSerum half-livesViral reboundAberrant DNA methylation of genes regulating CD4+ T cell HIV‐1 reservoir in women with HIV
Xu K, Zhang X, Asam K, Quach B, Page G, Konkle‐Parker D, Martinez C, Lahiri C, Topper E, Cohen M, Kassaye S, DeHovitz J, Kuniholm M, Archin N, Valizadeh A, Tien P, Marconi V, Hancock D, Johnson E, Aouizerat B. Aberrant DNA methylation of genes regulating CD4+ T cell HIV‐1 reservoir in women with HIV. Clinical And Translational Medicine 2025, 15: e70267. PMID: 40070009, PMCID: PMC11896887, DOI: 10.1002/ctm2.70267.Peer-Reviewed Original ResearchConceptsCD4+ T cellsHIV-1 reservoirHIV-1 latencyT cellsHIV-1Aberrant DNA methylationMechanisms of HIV-1 latencyViral replicationVirally suppressed womenDNA methylationHIV-1 integration sitesHIV-1 replicationMolecular targetsDifferentially methylated CpG sitesImmune defenceDNA methylation sequencingHost epigenetic landscapeDNA methylation sitesHIV-1 DNA integrationDifferentially methylated sitesHost genome integrityInterferon signaling genesCure HIVHost-virus interactionsCD4
2023
Single-cell epigenetic, transcriptional, and protein profiling of latent and active HIV-1 reservoir revealed that IKZF3 promotes HIV-1 persistence
Wei Y, Davenport T, Collora J, Ma H, Pinto-Santini D, Lama J, Alfaro R, Duerr A, Ho Y. Single-cell epigenetic, transcriptional, and protein profiling of latent and active HIV-1 reservoir revealed that IKZF3 promotes HIV-1 persistence. Immunity 2023, 56: 2584-2601.e7. PMID: 37922905, PMCID: PMC10843106, DOI: 10.1016/j.immuni.2023.10.002.Peer-Reviewed Original ResearchConceptsTranscription factor accessibilityHIV-1-infected cellsFactor accessibilityHIV-1 persistenceHeterogeneous cellular statesEpigenetic programsCellular programsCellular statesLatent HIV-1-infected cellsProliferation programProtein profilingSuppressive antiretroviral therapyHIV-1 eradicationHIV-1 reservoirCell deathProtein statesHIV-1 RNAAP-1HIV-1 DNASurface proteinsMechanistic interrogationEpigeneticsAntiretroviral therapyMemory CD4Effector differentiationRebound HIV-1 in cerebrospinal fluid after antiviral therapy interruption is mainly clonally amplified R5 T cell-tropic virus
Kincer L, Joseph S, Gilleece M, Hauser B, Sizemore S, Zhou S, Di Germanio C, Zetterberg H, Fuchs D, Deeks S, Spudich S, Gisslen M, Price R, Swanstrom R. Rebound HIV-1 in cerebrospinal fluid after antiviral therapy interruption is mainly clonally amplified R5 T cell-tropic virus. Nature Microbiology 2023, 8: 260-271. PMID: 36717718, PMCID: PMC10201410, DOI: 10.1038/s41564-022-01306-6.Peer-Reviewed Original ResearchConceptsCentral nervous systemT cell-tropic virusesInfected T cellsCerebrospinal fluidAntiretroviral therapyHIV-1Rebound virusViral loadT cellsMacrophage-tropic HIV-1CSF viral loadSuppressive antiretroviral therapyHIV-1 reservoirMacrophage-tropic virusesHigh viral loadWhite blood cellsTherapy interruptionLatent reservoirLymphoid systemNervous systemSystemic infectionVirus replicationBlood cellsTransient influxVirus
2021
The Clonal Expansion Dynamics of the HIV-1 Reservoir: Mechanisms of Integration Site-Dependent Proliferation and HIV-1 Persistence
Yeh YJ, Yang K, Razmi A, Ho YC. The Clonal Expansion Dynamics of the HIV-1 Reservoir: Mechanisms of Integration Site-Dependent Proliferation and HIV-1 Persistence. Viruses 2021, 13: 1858. PMID: 34578439, PMCID: PMC8473165, DOI: 10.3390/v13091858.Peer-Reviewed Original ResearchConceptsHIV-1-infected cellsHIV-1 latent reservoirAntiretroviral therapyHIV-1Cancer-related gene expressionHIV-1 promoterHIV-1 integration sitesLatent reservoirClonal expansionClonal expansion dynamicsCancer-related genesLong-term suppressive antiretroviral therapyHIV-1 promoter activitySuppressive antiretroviral therapyLow-level viremiaHIV-1 reservoirHIV-1 persistenceHIV-1 transcriptionCertain cancer-related genesViral reboundGene expressionRare caseLoss of functionTherapeutic agentsTumor suppressor geneModulating 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
2020
The single-cell landscape of immunological responses of CD4+ T cells in HIV versus severe acute respiratory syndrome coronavirus 2.
Collora JA, Liu R, Albrecht K, Ho YC. The single-cell landscape of immunological responses of CD4+ T cells in HIV versus severe acute respiratory syndrome coronavirus 2. Current Opinion In HIV And AIDS 2020, 16: 36-47. PMID: 33165008, PMCID: PMC8162470, DOI: 10.1097/coh.0000000000000655.Peer-Reviewed Original ResearchConceptsHIV-1 infectionSARS-CoV-2 infectionCD4 T cellsT cellsLymphoid tissueHIV-1SARS-CoV-2-specific CD4 T cellsAcute respiratory syndrome coronavirus 2 infectionHIV-1-specific CD4 T cellsSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionSevere SARS-CoV-2 infectionSevere acute respiratory syndrome coronavirus 2CD4 T-cell depletionSyndrome coronavirus 2 infectionAcute respiratory syndrome coronavirus 2CD4 T-cell lossFollicular helper T cellsHIV-1-infected cellsRespiratory syndrome coronavirus 2Coronavirus 2 infectionCytokine release syndromeT cell lossT-cell depletionHIV-1 reservoirProtective antibody responsesFeasibility and safety of research sigmoid colon biopsy in a cohort of Thai men who have sex with men with acute HIV-1
Chintanaphol M, Sacdalan C, Pinyakorn S, Rerknimitr R, Ridtitid W, Prueksapanich P, Sereti I, Schuetz A, Crowell TA, Colby DJ, Robb ML, Phanuphak N, Ananworanich J, Spudich SS, Kroon E. Feasibility and safety of research sigmoid colon biopsy in a cohort of Thai men who have sex with men with acute HIV-1. Journal Of Virus Eradication 2020, 6: 7-10. PMID: 32175085, PMCID: PMC7043900, DOI: 10.1016/s2055-6640(20)30011-x.Peer-Reviewed Original ResearchAcute HIV-1 infectionGut-associated lymphoid tissueHIV-1 reservoirSigmoid colon biopsiesAdverse eventsAE riskSigmoid colonColon biopsiesHIV-1CD4 T-cell depletionCD4 T-cell countAcute HIV-1Mild rectal bleedingAdverse event incidenceT-cell countsHigh viral replicationT-cell depletionHIV-1 infectionHIV-1 RNATime of biopsyIncidence rate ratiosRectal bleedingAbdominal discomfortEvent incidenceViral load
2019
Potential for early antiretroviral therapy to reduce central nervous system HIV-1 persistence.
Spudich S, Peterson J, Fuchs D, Price RW, Gisslen M. Potential for early antiretroviral therapy to reduce central nervous system HIV-1 persistence. AIDS 2019, 33 Suppl 2: s135-s144. PMID: 31789814, DOI: 10.1097/qad.0000000000002326.Peer-Reviewed Original ResearchConceptsHIV-1 infectionCentral nervous systemEarly antiretroviral therapyAntiretroviral therapyHIV-1 persistenceEarly treatmentInitiation of ARTCentral nervous inflammationEarly-treatment cohortHIV-1 exposureHIV-1 reservoirCourse of infectionClinical neurological diseaseCNS infectionHIV reservoirTreatment cohortsImmune activationCNS compartmentViral controlHIV-1Cerebrospinal fluidClinical reportsNervous systemEarly infectionNeurological diseasesDeep Sequencing Reveals Central Nervous System Compartmentalization in Multiple Transmitted/Founder Virus Acute HIV-1 Infection
Tovanabutra S, Sirijatuphat R, Pham PT, Bonar L, Harbolick EA, Bose M, Song H, Chang D, Oropeza C, O’Sullivan A, Balinang J, Kroon E, Colby DJ, Sacdalan C, Hellmuth J, Chan P, Prueksakaew P, Pinyakorn S, Jagodzinski LL, Sutthichom D, Pattamaswin S, de Souza M, Gramzinski RA, Kim JH, Michael NL, Robb ML, Phanuphak N, Ananworanich J, Valcour V, Kijak GH, Sanders-Buell E, Spudich S, Core T, Team T. Deep Sequencing Reveals Central Nervous System Compartmentalization in Multiple Transmitted/Founder Virus Acute HIV-1 Infection. Cells 2019, 8: 902. PMID: 31443253, PMCID: PMC6721674, DOI: 10.3390/cells8080902.Peer-Reviewed Original ResearchConceptsAcute HIV-1 infectionCentral nervous systemHIV-1 infectionCerebrospinal fluidCNS compartmentalizationHIV-1HIV-1 compartmentalizationHIV-1 exposureHIV-1 neuropathogenesisHIV-1 reservoirSingle-genome sequencingHIV reservoirFounder virusesRemission strategiesNeurological impairmentNervous systemF infectionsViral replicationInfectionPotential long-term implicationsNext-generation sequencingEnvelope geneTissue compartmentsF variantLong-term implications
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