2024
Neurosymptomatic HIV-1 CSF escape is associated with replication in CNS T cells and inflammation
Kincer L, Dravid A, Trunfio M, Calcagno A, Zhou S, Vercesi R, Spudich S, Gisslen M, Price R, Cinque P, Joseph S. Neurosymptomatic HIV-1 CSF escape is associated with replication in CNS T cells and inflammation. Journal Of Clinical Investigation 2024, 134: e176358. PMID: 39352388, PMCID: PMC11444166, DOI: 10.1172/jci176358.Peer-Reviewed Original ResearchConceptsHIV-1 RNACD4+ T cellsHIV-1 populationsAntiretroviral therapyHIV-1T cellsCerebrospinal fluidCSF escapeCNS inflammationDetectable HIV-1 RNAImprovement of neurological symptomsAssociated with viral suppressionUntreated chronic infectionDrug-resistant virusesProgressive neurological deficitsCNS T cellsART regimenViral suppressionChronic infectionNeurological deficitsNeurological symptomsInflammatory biomarkersClinical consequencesVirus expressionPrimary infectionHIV-1–infected T cell clones are shared across cerebrospinal fluid and blood during ART
Wang M, Yoon J, Reisert H, Das B, Orlinick B, Chiarella J, Halvas E, Mellors J, Pang A, Barakat L, Fikrig M, Cyktor J, Kluger Y, Spudich S, Corley M, Farhadian S. HIV-1–infected T cell clones are shared across cerebrospinal fluid and blood during ART. JCI Insight 2024, 9: e176208. PMID: 38587074, PMCID: PMC11128194, DOI: 10.1172/jci.insight.176208.Peer-Reviewed Original ResearchConceptsT cell clonesT cell receptorCerebrospinal fluidT cellsHIV-1Infected T-cell clonesCentral memory T cellsCD4 T-cell clonesDetectable HIV RNAMemory T cellsHIV-1 RNAInfected T cellsCNS reservoirsHIV persistenceHIV reservoirHIV RNAHIV cureReservoir cellsPWHTissue compartmentsBloodCNSUninfected controlsCD4Infected cells
2023
CD4dimCD8bright T cells are inversely associated with neuro-inflammatory markers among people with HIV
Albalawi Y, Shull T, Virdi A, Subra C, Mitchell J, Slike B, Jian N, Krebs S, Sacdalan C, Ratnaratorn N, Hsu D, Phanuphak N, Spudich S, Trautmann L, Al-Harthi L. CD4dimCD8bright T cells are inversely associated with neuro-inflammatory markers among people with HIV. AIDS 2023, 38: 1-7. PMID: 37792358, PMCID: PMC10715695, DOI: 10.1097/qad.0000000000003743.Peer-Reviewed Original ResearchConceptsCombination antiretroviral therapyT cellsWeeks 0CD4-CD8Cerebrospinal fluidImmune activationSoluble markersSuppressive combination antiretroviral therapyPeripheral blood T cellsNeuro-inflammatory markersSubset of CD8Anti-inflammatory propertiesBlood T cellsConfidence intervalsPlasma of peopleT-cell typeCART initiationCSF neopterinPlasma RANTESAntiretroviral therapyWeek 24IP-10IL-6Lumbar punctureIL-8Rebound 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
2022
Long-term antiretroviral therapy initiated in acute HIV infection prevents residual dysfunction of HIV-specific CD8+ T cells
Takata H, Kakazu J, Mitchell J, Kroon E, Colby D, Sacdalan C, Bai H, Ehrenberg P, Geretz A, Buranapraditkun S, Pinyakorn S, Intasan J, Tipsuk S, Suttichom D, Prueksakaew P, Chalermchai T, Chomchey N, Phanuphak N, de Souza M, Michael N, Robb M, Haddad E, Crowell T, Vasan S, Valcour V, Douek D, Thomas R, Rolland M, Chomont N, Ananworanich J, Trautmann L, Teeratakulpisarn N, Pattanachaiwit S, Sriplienchan S, Tantivitayakul P, Kanaprach R, Ruxrungtham K, Dumrongpisutikul N, Rojnuckarin P, Chottanapund S, Poltavee K, Luekasemsuk T, Savadsuk H, Puttamsawin S, Benjapornpong K, Ratnaratorn N, Tangnaree K, Munkong C, Thaimanee R, Eamyoung P, Ubolyam S, Lerdlum S, Manasnayakorn S, Rerknimitr R, Sirivichayakul S, Wattanaboonyongcharoen P, Cowden J, Schuetz A, Akapirat S, Churikanont N, Getchalarat S, Hsu D, Turk E, Butterworth O, Milazzo M, Eller L, Ake J, Eller L, Spudich S, Fox L, Ratto-Kim S, DeGruttola V, Chinvarun Y, Sithinamsuwan P, Fletcher J, Shiramizu B, Schuetz A. Long-term antiretroviral therapy initiated in acute HIV infection prevents residual dysfunction of HIV-specific CD8+ T cells. EBioMedicine 2022, 84: 104253. PMID: 36088683, PMCID: PMC9471490, DOI: 10.1016/j.ebiom.2022.104253.Peer-Reviewed Original ResearchConceptsHIV-specific CD8Long-term antiretroviral therapyFunctional HIV-specific CD8Acute HIV infectionAntiretroviral therapyT cellsART initiationHIV infectionResidual dysfunctionVitro recallTCF-1 expressionChronic HIV infectionHIV remission strategiesT cell numbersT cell responsesInfection ex vivoStem cell-like propertiesCell numberCell-like propertiesART interruptionSpontaneous controllersViral reboundAcute infectionHIV remissionRemission strategiesHIV viral transcription and immune perturbations in the CNS of people with HIV despite ART
Farhadian SF, Lindenbaum O, Zhao J, Corley MJ, Im Y, Walsh H, Vecchio A, Garcia-Milian R, Chiarella J, Chintanaphol M, Calvi R, Wang G, Ndhlovu LC, Yoon J, Trotta D, Ma S, Kluger Y, Spudich S. HIV viral transcription and immune perturbations in the CNS of people with HIV despite ART. JCI Insight 2022, 7: e160267. PMID: 35801589, PMCID: PMC9310520, DOI: 10.1172/jci.insight.160267.Peer-Reviewed Original ResearchConceptsCerebrospinal fluidHIV infectionHIV-1-infected cellsCNS viral persistenceCentral memory CD4T-cell abnormalitiesHIV-1 RNAMicroglia-like cellsT cell activationSystemic viral suppressionAbnormal CD8HIV neuropathogenesisViral suppressionMemory CD4CNS reservoirsImmune perturbationsExperience elevated ratesNeuroimmune effectsPeripheral bloodNeurological impairmentViral persistenceT cellsCell abnormalitiesUninfected controlsCell activationInfection and inflammation: New perspectives on Alzheimer's disease
Whitson HE, Colton C, Khoury J, Gate D, Goate A, Heneka MT, Kaddurah-Daouk R, Klein RS, Shinohara ML, Sisodia S, Spudich SS, Stevens B, Tanzi R, Ting JP, Garden G, members S, Aiello A, Chiba-Falek O, Heitman J, Johnson K, Luftig M, Moseman A, Rawls J, Shinohara M, Swanstrom R, Terrando N. Infection and inflammation: New perspectives on Alzheimer's disease. Brain Behavior & Immunity - Health 2022, 22: 100462. PMID: 36118272, PMCID: PMC9475126, DOI: 10.1016/j.bbih.2022.100462.Peer-Reviewed Original ResearchDisease Research CenterAlzheimer's diseaseAD pathogenesisSelf-reactive T cellsDisease pathologyCOVID-19 patientsAlzheimer's Disease Research CenterAlzheimer's disease pathologyNeurologic symptomsInflammatory cellsT cellsMouse modelCurrent evidenceHuman immunityAlois AlzheimerMetabolic alterationsCommensal microbesFungal infectionsInfectionDiseasePotential involvementInflammationPathogenesisFunctional stateNeuroinflammation
2021
Cerebrospinal fluid CD4+ T cell infection in humans and macaques during acute HIV-1 and SHIV infection
Sharma V, Creegan M, Tokarev A, Hsu D, Slike BM, Sacdalan C, Chan P, Spudich S, Ananworanich J, Eller MA, Krebs SJ, Vasan S, Bolton DL. Cerebrospinal fluid CD4+ T cell infection in humans and macaques during acute HIV-1 and SHIV infection. PLOS Pathogens 2021, 17: e1010105. PMID: 34874976, PMCID: PMC8683024, DOI: 10.1371/journal.ppat.1010105.Peer-Reviewed Original ResearchConceptsT-cell infectionCentral nervous systemAcute HIV-1HIV-1 replicationCerebrospinal fluidT cellsHIV-1Peripheral bloodViral reservoirCell infectionBroad immune activationCerebrospinal fluid CD4CNS viral reservoirCSF T cellsHIV-1 cureActive viral transcriptionLong-term inflammationViral RNACSF CD4Early neuroinflammationAntiretroviral therapyHuman cerebrospinal fluidAcute infectionImmune activationCNS compartmentAbrupt and altered cell-type specific DNA methylation profiles in blood during acute HIV infection persists despite prompt initiation of ART
Corley MJ, Sacdalan C, Pang APS, Chomchey N, Ratnaratorn N, Valcour V, Kroon E, Cho KS, Belden AC, Colby D, Robb M, Hsu D, Spudich S, Paul R, Vasan S, Ndhlovu LC, . Abrupt and altered cell-type specific DNA methylation profiles in blood during acute HIV infection persists despite prompt initiation of ART. PLOS Pathogens 2021, 17: e1009785. PMID: 34388205, PMCID: PMC8386872, DOI: 10.1371/journal.ppat.1009785.Peer-Reviewed Original ResearchConceptsAntiretroviral therapyT lymphocytesCD4/CD8 ratioHIV infection cohortHost epigenetic landscapeAcute HIV infectionSpecific DNA methylation profileInfection cohortInfection HIVCD4 countCD8 ratioHIV infectionPrompt initiationViral loadHIV medicineViral persistenceEarly initiationT cellsHIV-1Disease pathogenesisClinical phenotypeMonocytesCD4HIVLymphocytes
2018
Human Immunodeficiency Virus Type 1 RNA Detected in the Central Nervous System (CNS) After Years of Suppressive Antiretroviral Therapy Can Originate from a Replicating CNS Reservoir or Clonally Expanded Cells
Joseph SB, Kincer LP, Bowman NM, Evans C, Vinikoor MJ, Lippincott CK, Gisslén M, Spudich S, Menezes P, Robertson K, Archin N, Kashuba A, Eron JJ, Price RW, Swanstrom R. Human Immunodeficiency Virus Type 1 RNA Detected in the Central Nervous System (CNS) After Years of Suppressive Antiretroviral Therapy Can Originate from a Replicating CNS Reservoir or Clonally Expanded Cells. Clinical Infectious Diseases 2018, 69: 1345-1352. PMID: 30561541, PMCID: PMC6938202, DOI: 10.1093/cid/ciy1066.Peer-Reviewed Original ResearchConceptsCentral nervous systemHIV-1 RNA concentrationsAntiretroviral therapySuppressive antiretroviral therapyCerebrospinal fluidCNS reservoirsCSF escapeCSF HIV-1 RNA concentrationsCentral nervous system reservoirYears of ARTHuman immunodeficiency virus type 1 (HIV-1) populationHuman immunodeficiency virus type 1 (HIV-1) RNAStable antiretroviral therapyHIV-1 RNAMacrophages/microgliaInfected T cellsRNA concentrationViral envelope sequencesType 1 populationViral populationsViral suppressionMacrophage-tropicAsymptomatic participantsMultiple time pointsT cells
2017
High Number of Activated CD8+ T Cells Targeting HIV Antigens Are Present in Cerebrospinal Fluid in Acute HIV Infection
Kessing CF, Spudich S, Valcour V, Cartwright P, Chalermchai T, Fletcher JL, Takata H, Nichols C, Josey B, Slike B, Krebs S, Sailsuta N, Lerdlum S, Jagodzinski L, Tipsuk S, Suttichom D, Rattanamanee S, Zetterberg H, Hellmuth J, Phanuphak N, Robb M, Michael N, Ananworanich J, Trautmann L. High Number of Activated CD8+ T Cells Targeting HIV Antigens Are Present in Cerebrospinal Fluid in Acute HIV Infection. JAIDS Journal Of Acquired Immune Deficiency Syndromes 2017, 75: 108-117. PMID: 28177966, PMCID: PMC5388590, DOI: 10.1097/qai.0000000000001301.Peer-Reviewed Original ResearchConceptsAcute HIV infectionCD8 T cellsChronic HIV infectionHIV infectionT cellsCerebrospinal fluidCD8 T cell effector functionsHIV-specific CD8 T cellsCentral nervous system infiltrationT cell effector functionT cell receptor repertoireCSF HIV RNACombination antiretroviral therapyTCR Vbeta repertoireCell effector functionsCell receptor repertoireHIV specificitiesAntiretroviral therapyCNS inflammationHIV RNAVbeta repertoireMicroglial activationActivated CD8HIV antigenHIV epitopesCROI 2017: Neurologic Complications of HIV Infection.
Spudich SS, Ances BM. CROI 2017: Neurologic Complications of HIV Infection. Topics In Antiviral Medicine 2017, 25: 69-76. PMID: 28598791, PMCID: PMC5677044.Peer-Reviewed Original ResearchConceptsEarly HIV infectionHIV infectionCentral nervous systemAntiretroviral therapyCNS HIV infectionPotential viral reservoirAntiretroviral regimensSuppressive therapyVirologic controlNeurologic complicationsBrain macrophagesOpportunistic infectionsViral reservoirCognitive screening testsMicroglial cellsChronic infectionRisk factorsNeurocognitive disordersT cellsChoroid plexusNervous systemCognitive impairmentNumerous cohortsScreening testLongitudinal evaluation
2016
Immune Activation and HIV-Specific CD8+ T Cells in Cerebrospinal Fluid of HIV Controllers and Noncontrollers
Ganesh A, Lemongello D, Lee E, Peterson J, McLaughlin BE, Ferre AL, Gillespie GM, Fuchs D, Deeks SG, Hunt PW, Price RW, Spudich SS, Shacklett BL. Immune Activation and HIV-Specific CD8+ T Cells in Cerebrospinal Fluid of HIV Controllers and Noncontrollers. AIDS Research And Human Retroviruses 2016, 32: 791-800. PMID: 27019338, PMCID: PMC4971411, DOI: 10.1089/aid.2015.0313.Peer-Reviewed Original ResearchMeSH KeywordsADP-ribosyl Cyclase 1Anti-HIV AgentsAntiretroviral Therapy, Highly ActiveCD4 Lymphocyte CountCD8-Positive T-LymphocytesDisease ResistanceGene ExpressionHIV InfectionsHIV-1HLA-DR AntigensHost-Pathogen InteractionsHumansLeukocyte Common AntigensLymphocyte ActivationReceptors, CCR5Receptors, CCR7RNA, ViralViral LoadViremiaConceptsCentral nervous systemHIV controllersAntiretroviral therapyT cellsCerebrospinal fluidViral loadCopies/HIV-specific T cellsMajor histocompatibility complex class IActivation markers CD38CSF viral loadHIV-specific CD8Undetectable plasma viremiaExpression of CCR5Majority of HIVPlasma viral loadEffector memory cellsHIV-negative controlsHistocompatibility complex class IAbsence of therapyComplex class ILong-term controlPlasma viremiaElite controllersHIV infectionVirological and immunological characteristics of HIV-infected individuals at the earliest stage of infection
Ananworanich J, Sacdalan CP, Pinyakorn S, Chomont N, Souza M, Luekasemsuk T, Schuetz A, Krebs SJ, Dewar R, Jagodzinski L, Ubolyam S, Trichavaroj R, Tovanabutra S, Spudich S, Valcour V, Sereti I, Michael N, Robb M, Phanuphak P, Kim JH, Phanuphak N, Group O. Virological and immunological characteristics of HIV-infected individuals at the earliest stage of infection. Journal Of Virus Eradication 2016, 2: 43-48. PMID: 26889497, PMCID: PMC4754199, DOI: 10.1016/s2055-6640(20)30688-9.Peer-Reviewed Original ResearchCD4/CD8 ratioAcute HIV infectionWeeks of ARTCD4 cell countFiebig ICD8 ratioT cellsThai Red Cross Anonymous ClinicCell countEarly acute HIV infectionPlasma interleukin-6 levelsImmune activation levelsLow HIV burdenLow HIV RNALow immune activationMedian HIV DNAPlasma sCD14 levelsMedian CD4 countInterleukin-6 levelsYears of ARTI individualsAHI participantsAnonymous ClinicFiebig stagesCD4 count
2015
Phenotypic Correlates of HIV-1 Macrophage Tropism
Arrildt KT, LaBranche CC, Joseph SB, Dukhovlinova EN, Graham WD, Ping LH, Schnell G, Sturdevant CB, Kincer LP, Mallewa M, Heyderman RS, Van Rie A, Cohen MS, Spudich S, Price RW, Montefiori DC, Swanstrom R. Phenotypic Correlates of HIV-1 Macrophage Tropism. Journal Of Virology 2015, 89: 11294-11311. PMID: 26339058, PMCID: PMC4645658, DOI: 10.1128/jvi.00946-15.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralCD4 AntigensCD4-Positive T-LymphocytesCell Line, TumorHEK293 CellsHIV Envelope Protein gp120HIV Envelope Protein gp160HIV Envelope Protein gp41HIV InfectionsHIV-1HumansMacrophagesReceptors, CCR5Recombinant ProteinsViral TropismVirus InternalizationConceptsT cell-tropic virusesT-tropic virusesMonocyte-derived macrophagesM-tropic virusesMacrophage-tropic virusesV1/V2 regionSoluble CD4Central nervous systemHIV-1Chronic infectionT cellsMacrophage-tropic HIV-1 variantsNervous systemM-tropic HIV-1HIV-1 env geneEnv proteinV2 regionT-cell tropicHIV-1 variantsCD4-bound conformationMacrophage-tropicMacrophage tropismM-tropicSurface CD4CD4
2014
Progressive increase in central nervous system immune activation in untreated primary HIV-1 infection
Suh J, Sinclair E, Peterson J, Lee E, Kyriakides TC, Li FY, Hagberg L, Fuchs D, Price RW, Gisslen M, Spudich S. Progressive increase in central nervous system immune activation in untreated primary HIV-1 infection. Journal Of Neuroinflammation 2014, 11: 199. PMID: 25465205, PMCID: PMC4263211, DOI: 10.1186/s12974-014-0199-y.Peer-Reviewed Original ResearchConceptsPrimary HIV-1 infectionHIV-1 infectionCSF neopterinCerebrospinal fluidT cellsHIV infectionCentral nervous system immune activationUntreated primary HIV-1 infectionBaseline levelsEarly HIV-1 infectionCSF neopterin concentrationsNervous system inflammationMixed effects modelsCluster of differentiationMajority of subjectsCNS inflammationSystem inflammationAverage followNeopterin concentrationsHIV transmissionImmune activationLumbar punctureResultsA totalIntrathecal inflammationNatural course
2013
Cellular Composition of Cerebrospinal Fluid in HIV-1 Infected and Uninfected Subjects
Ho EL, Ronquillo R, Altmeppen H, Spudich SS, Price RW, Sinclair E. Cellular Composition of Cerebrospinal Fluid in HIV-1 Infected and Uninfected Subjects. PLOS ONE 2013, 8: e66188. PMID: 23822975, PMCID: PMC3688831, DOI: 10.1371/journal.pone.0066188.Peer-Reviewed Original ResearchConceptsT cellsCerebrospinal fluidHIV infectionMajor cellular componentCD8 ratioUninfected subjectsNK cellsB cellsHIV-1 infectionCellular compositionMulti-parameter flow cytometrySpectrum of diseaseCentral nervous systemCSF CD4Lymphocyte subsetsPeripheral lossPeripheral bloodHealthy controlsHIV-1Absolute countsCD4HIVPreferential traffickingNervous systemCD8