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 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 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 expressionCD4Integration site–dependent HIV-1 promoter activity shapes host chromatin conformation
Collora J, Ho Y. Integration site–dependent HIV-1 promoter activity shapes host chromatin conformation. Genome Research 2023, 33: 891-906. PMID: 37295842, PMCID: PMC10519397, DOI: 10.1101/gr.277698.123.Peer-Reviewed Original ResearchInhibition 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 ResearchConceptsHIV-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 candidatesSingle-cell transcriptional landscapes reveal HIV-1–driven aberrant host gene transcription as a potential therapeutic target
Liu R, Yeh YJ, Varabyou A, Collora JA, Sherrill-Mix S, Talbot CC, Mehta S, Albrecht K, Hao H, Zhang H, Pollack RA, Beg SA, Calvi RM, Hu J, Durand CM, Ambinder RF, Hoh R, Deeks SG, Chiarella J, Spudich S, Douek DC, Bushman FD, Pertea M, Ho YC. Single-cell transcriptional landscapes reveal HIV-1–driven aberrant host gene transcription as a potential therapeutic target. Science Translational Medicine 2020, 12 PMID: 32404504, PMCID: PMC7453882, DOI: 10.1126/scitranslmed.aaz0802.Peer-Reviewed Original ResearchConceptsHost gene transcriptionGene transcriptionLong terminal repeatHIV-1 reactivationCellular factorsIntegration sitesNonsense-mediated RNA decaySingle-cell transcriptional landscapePotential therapeutic targetSingle-cell transcriptome analysisHIV-1-host interactionsHIV-1HIV-1 promoterTherapeutic targetHIV-1 5' long terminal repeatRNA decayTranscriptional landscapeHIV-1-infected individualsHIV-1-infected cellsTranscriptome analysisAberrant transcriptionRNA transcriptionHost RNACellular survivalTranscription pathway
2024
The single-cell opioid responses in the context of HIV (SCORCH) consortium
Ament S, Campbell R, Lobo M, Receveur J, Agrawal K, Borjabad A, Byrareddy S, Chang L, Clarke D, Emani P, Gabuzda D, Gaulton K, Giglio M, Giorgi F, Gok B, Guda C, Hadas E, Herb B, Hu W, Huttner A, Ishmam M, Jacobs M, Kelschenbach J, Kim D, Lee C, Liu S, Liu X, Madras B, Mahurkar A, Mash D, Mukamel E, Niu M, O’Connor R, Pagan C, Pang A, Pillai P, Repunte-Canonigo V, Ruzicka W, Stanley J, Tickle T, Tsai S, Wang A, Wills L, Wilson A, Wright S, Xu S, Yang J, Zand M, Zhang L, Zhang J, Akbarian S, Buch S, Cheng C, Corley M, Fox H, Gerstein M, Gummuluru S, Heiman M, Ho Y, Kellis M, Kenny P, Kluger Y, Milner T, Moore D, Morgello S, Ndhlovu L, Rana T, Sanna P, Satterlee J, Sestan N, Spector S, Spudich S, Tilgner H, Volsky D, White O, Williams D, Zeng H. The single-cell opioid responses in the context of HIV (SCORCH) consortium. Molecular Psychiatry 2024, 1-12. PMID: 38879719, DOI: 10.1038/s41380-024-02620-7.Peer-Reviewed Original ResearchContext of human immunodeficiency virusHuman immunodeficiency virusSubstance use disordersOpioid responseAnimal modelsEffects of substance use disordersOpioid pain medicationsPrevalence of co-morbid conditionsChronic pain syndromesStage of diseaseCell typesAffected cell typesCo-morbid conditionsPain syndromeImmunodeficiency virusPain medicationOpioid addictionIncreased riskRisk factorsHuman cohortsDrug addictionBrain tissue collectionBrain cell typesTissue collectionSingle-cell level
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 ResearchConceptsSurface protein expressionMultiomics approachATAC-seqProtein expressionTranscription factor activityProtein levelsRNA mappingRNA-seqBioinformatics analysisHIV-1-infected cellsFalse positive discoveriesBiological insightsBulk transcriptomeFactor activityDNA amplificationExpressionCellsTranscriptomeTherapeutic strategiesEpigeneticsDiscoveryDNA PCRRNADNAHIV-1
2022
Interferon opens up: HIV-induced inflammation reconfigures 3D chromatin conformation and affects where HIV integrates
Wei Y, Ho Y. Interferon opens up: HIV-induced inflammation reconfigures 3D chromatin conformation and affects where HIV integrates. Molecular Cell 2022, 82: 4585-4587. PMID: 36525953, PMCID: PMC9925257, DOI: 10.1016/j.molcel.2022.11.013.Peer-Reviewed Original ResearchThe loud minority: Transcriptionally active HIV-1-infected cells survive, proliferate, and persist
Collora JA, Ho YC. The loud minority: Transcriptionally active HIV-1-infected cells survive, proliferate, and persist. Cell 2022, 185: 227-229. PMID: 35063069, PMCID: PMC9195179, DOI: 10.1016/j.cell.2021.12.038.Peer-Reviewed Original Research
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 ResearchThe 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 geneRestriction of SARS-CoV-2 replication by targeting programmed −1 ribosomal frameshifting
Sun Y, Abriola L, Niederer RO, Pedersen SF, Alfajaro MM, Silva Monteiro V, Wilen CB, Ho YC, Gilbert WV, Surovtseva YV, Lindenbach BD, Guo JU. Restriction of SARS-CoV-2 replication by targeting programmed −1 ribosomal frameshifting. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2023051118. PMID: 34185680, PMCID: PMC8256030, DOI: 10.1073/pnas.2023051118.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 replicationSARS-CoV-2Severe acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Syndrome coronavirus 2Vero E6 cellsHigh-throughput compound screenOpen reading frame 1bEffective antiviral strategiesCoronavirus 2E6 cellsAntiviral strategiesViral gene expressionCompound screenFluoroquinolone antibacterialsFrame 1bGene expressionMeasuring the size and decay dynamics of the HIV-1 latent reservoir
Liu R, Catalano AA, Ho YC. Measuring the size and decay dynamics of the HIV-1 latent reservoir. Cell Reports Medicine 2021, 2: 100249. PMID: 33948579, PMCID: PMC8080242, DOI: 10.1016/j.xcrm.2021.100249.Peer-Reviewed Original ResearchShock-and-kill versus block-and-lock: Targeting the fluctuating and heterogeneous HIV-1 gene expression
Yeh YJ, Ho YC. Shock-and-kill versus block-and-lock: Targeting the fluctuating and heterogeneous HIV-1 gene expression. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2103692118. PMID: 33758027, PMCID: PMC8072369, DOI: 10.1073/pnas.2103692118.Peer-Reviewed Original Research
2020
The XPB Subunit of the TFIIH Complex Plays a Critical Role in HIV-1 Transcription, and XPB Inhibition by Spironolactone Prevents HIV-1 Reactivation from Latency
Mori L, Jenike K, Yeh YJ, Lacombe B, Li C, Getzler A, Mediouni S, Cameron M, Pipkin M, Ho YC, Ramirez BC, Valente S. The XPB Subunit of the TFIIH Complex Plays a Critical Role in HIV-1 Transcription, and XPB Inhibition by Spironolactone Prevents HIV-1 Reactivation from Latency. Journal Of Virology 2020, 95: 10.1128/jvi.01247-20. PMID: 33239456, PMCID: PMC7851559, DOI: 10.1128/jvi.01247-20.Peer-Reviewed Original ResearchAntiretroviral therapyHIV-1 transcriptionHIV transcriptionTreatment interruptionCell line modelsViral reservoirAbsence of ARTRapid viral reboundAcute HIV infectionHIV-1 reactivationChronic immune activationHIV-1 latencyLong-term treatmentHIV transcriptional regulationConcentrations of spironolactoneFunctional cure approachesCure approachesCellular mRNA expressionSP treatmentMechanism of actionHIV-1 genomeAldosterone antagonistsViral reboundFunctional cureHIV reactivationThe 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 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 ResearchSARS-CoV-2: A Storm is Raging
Pedersen SF, Ho YC. SARS-CoV-2: A Storm is Raging. Journal Of Clinical Investigation 2020, 130: 2202-2205. PMID: 32217834, PMCID: PMC7190904, DOI: 10.1172/jci137647.Peer-Reviewed Original ResearchConceptsSevere COVID-19Severe acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2COVID-19Respiratory syndrome coronavirus 2Syndrome coronavirus 2IFN-γ expressionCoronavirus infectious diseaseCytokine levelsCytokine stormRespiratory distressCoronavirus 2Immune therapeuticsUnfavorable outcomeT cellsImmunological characteristicsVaccine designInfectious diseasesLymphopeniaCD4AdmissionDiseaseThe 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 ResearchConceptsHIV-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