Featured Publications
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 ResearchMeSH KeywordsCD4-Positive T-LymphocytesEpigenesis, GeneticHIV InfectionsHIV-1HumansIkaros Transcription FactorTranscription Factor AP-1Virus LatencyConceptsTranscription 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 differentiationSingle-cell multiomics reveals persistence of HIV-1 in expanded cytotoxic T cell clones
Collora JA, Liu R, Pinto-Santini D, Ravindra N, Ganoza C, Lama JR, Alfaro R, Chiarella J, Spudich S, Mounzer K, Tebas P, Montaner LJ, van Dijk D, Duerr A, Ho YC. Single-cell multiomics reveals persistence of HIV-1 in expanded cytotoxic T cell clones. Immunity 2022, 55: 1013-1031.e7. PMID: 35320704, PMCID: PMC9203927, DOI: 10.1016/j.immuni.2022.03.004.Peer-Reviewed Original ResearchConceptsHIV-1 eradicationHIV-1 RNAHIV-1Effector memory Th1 cellsHIV-1-infected individualsHIV-1-infected CD4Clonal expansionCell clonesMemory Th1 cellsCell clonal expansionPersistent antigenAntiretroviral therapyViral suppressionCytotoxic CD4Cytotoxic TTh1 cellsAntigen stimulationClonal expansion dynamicsUninfected individualsSurface protein expressionTNF responseUnstimulated conditionsTCR sequencesProtein expressionCD4Inhibition of a Chromatin and Transcription Modulator, SLTM, Increases HIV-1 Reactivation Identified by a CRISPR Inhibition Screen
Pedersen SF, Collora JA, Kim RN, Yang K, Razmi A, Catalano AA, Yeh YJ, Mounzer K, Tebas P, Montaner LJ, Ho YC. Inhibition of a Chromatin and Transcription Modulator, SLTM, Increases HIV-1 Reactivation Identified by a CRISPR Inhibition Screen. Journal Of Virology 2022, 96: e00577-22. PMID: 35730977, PMCID: PMC9278143, DOI: 10.1128/jvi.00577-22.Peer-Reviewed Original ResearchConceptsHIV-1-infected cellsHIV-1 reactivationT cell clonesHIV-1HIV-1 protein expressionAntiretroviral therapyDrug treatmentProtein expressionInfected cellsInfected individualsHIV-1-infected individualsCell clonesEffective antiretroviral therapyHIV-1 cureLong-term therapyHIV-1 gene expressionHIV-1 persistenceHIV-1 provirusHIV-1 transcriptionImmune cell killingNovel therapeutic targetCell deathLatent reservoirImmune cellsT cellsFilgotinib suppresses HIV-1-driven gene transcription by inhibiting HIV-1 splicing and T cell activation
Yeh YJ, Jenike KM, Calvi RM, Chiarella J, Hoh R, Deeks SG, Ho YC. Filgotinib suppresses HIV-1-driven gene transcription by inhibiting HIV-1 splicing and T cell activation. Journal Of Clinical Investigation 2020, 130: 4969-4984. PMID: 32573496, PMCID: PMC7456222, DOI: 10.1172/jci137371.Peer-Reviewed Original ResearchMeSH KeywordsCD4-Positive T-LymphocytesHIV InfectionsHIV-1HumansJurkat CellsLymphocyte ActivationPyridinesRNA SplicingTranscription, GeneticTriazolesConceptsHIV-1 reactivationHIV-1-infected cellsT cell activationImmune activationHIV-1-induced immune activationCell activationHIV-1 RNA transcriptionHIV-1-infected individualsDrug screensEffective antiretroviral therapyHIV-1 transcriptionFilgotinib treatmentImmune exhaustionAntiretroviral therapyCell line modelsCancer-related gene expressionHIV-1 splicingViral antigensT cellsDrug treatmentHigh-throughput drug screensJAK inhibitorsFilgotinibDruggable targetsDrug candidates
2023
Single-cell multiomic understanding of HIV-1 reservoir at epigenetic, transcriptional, and protein levels
Wong M, Wei Y, Ho Y. Single-cell multiomic understanding of HIV-1 reservoir at epigenetic, transcriptional, and protein levels. Current Opinion In HIV And AIDS 2023, 18: 246-256. PMID: 37535039, PMCID: PMC10442869, DOI: 10.1097/coh.0000000000000809.Peer-Reviewed Original ResearchMeSH KeywordsCD4-Positive T-LymphocytesEpigenesis, GeneticHIV InfectionsHIV-1HumansMultiomicsRNA, ViralVirus LatencyConceptsSurface protein expressionMultiomics approachATAC-seqProtein expressionTranscription factor activityProtein levelsRNA mappingRNA-seqBioinformatics analysisHIV-1-infected cellsFalse positive discoveriesBiological insightsBulk transcriptomeFactor activityDNA amplificationExpressionCellsTranscriptomeTherapeutic strategiesEpigeneticsDiscoveryDNA PCRRNADNAHIV-1
2021
A multidimensional HIV-1 persistence model for clonal expansion and viral rebound in vitro
Eshetu A, Ho YC. A multidimensional HIV-1 persistence model for clonal expansion and viral rebound in vitro. Cell Reports Methods 2021, 1: 100134. PMID: 35475216, PMCID: PMC9017154, DOI: 10.1016/j.crmeth.2021.100134.Peer-Reviewed Original Research
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 ResearchMeSH KeywordsAnimalsCD4-Positive T-LymphocytesCOVID-19CytokinesHIV InfectionsHumansPandemicsSARS-CoV-2ConceptsHIV-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 responsesRecommendations for measuring HIV reservoir size in cure-directed clinical trials
Abdel-Mohsen M, Richman D, Siliciano RF, Nussenzweig MC, Howell BJ, Martinez-Picado J, Chomont N, Bar KJ, Yu XG, Lichterfeld M, Alcami J, Hazuda D, Bushman F, Siliciano JD, Betts MR, Spivak AM, Planelles V, Hahn BH, Smith DM, Ho YC, Buzon MJ, Gaebler C, Paiardini M, Li Q, Estes JD, Hope TJ, Kostman J, Mounzer K, Caskey M, Fox L, Frank I, Riley JL, Tebas P, Montaner LJ. Recommendations for measuring HIV reservoir size in cure-directed clinical trials. Nature Medicine 2020, 26: 1339-1350. PMID: 32895573, PMCID: PMC7703694, DOI: 10.1038/s41591-020-1022-1.Peer-Reviewed Original ResearchMeSH KeywordsAnti-Retroviral AgentsCD4-Positive T-LymphocytesClinical Trials as TopicDisease ReservoirsHIV InfectionsHIV-1HumansMass ScreeningViral LoadVirus LatencyThe forces driving clonal expansion of the HIV-1 latent reservoir
Liu R, Simonetti FR, Ho YC. The forces driving clonal expansion of the HIV-1 latent reservoir. Virology Journal 2020, 17: 4. PMID: 31910871, PMCID: PMC6947923, DOI: 10.1186/s12985-019-1276-8.Peer-Reviewed Original ResearchMeSH KeywordsCD4-Positive T-LymphocytesHIV InfectionsHIV-1HumansProvirusesViral LoadVirus IntegrationVirus LatencyVirus ReplicationConceptsHIV-1-infected cellsHIV-1 latent reservoirLatent reservoirAntiretroviral therapyClonal expansionViral reboundHomeostatic proliferationAntigen-specific CD4HIV-1 eradicationHIV-1 replicationT cell functionHIV-1 provirusCertain cancer-related genesCytokine profileAntigen exposureViral loadExhaustion phenotypeLymphoid tissueT cellsClonal expansion dynamicsImmune clearanceCancer-related genesViral expressionCell functionUndetectable levels
2013
Replication-Competent Noninduced Proviruses in the Latent Reservoir Increase Barrier to HIV-1 Cure
Ho YC, Shan L, Hosmane NN, Wang J, Laskey SB, Rosenbloom DI, Lai J, Blankson JN, Siliciano JD, Siliciano RF. Replication-Competent Noninduced Proviruses in the Latent Reservoir Increase Barrier to HIV-1 Cure. Cell 2013, 155: 540-551. PMID: 24243014, PMCID: PMC3896327, DOI: 10.1016/j.cell.2013.09.020.Peer-Reviewed Original Research