2022
Nervous system consequences of COVID-19
Spudich S, Nath A. Nervous system consequences of COVID-19. Science 2022, 375: 267-269. PMID: 35050660, DOI: 10.1126/science.abm2052.Peer-Reviewed Original Research
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 compartmentCerebrospinal Fluid Viral Load Across the Spectrum of Untreated Human Immunodeficiency Virus Type 1 (HIV-1) Infection: A Cross-Sectional Multicenter Study
Ulfhammer G, Edén A, Antinori A, Brew BJ, Calcagno A, Cinque P, De Zan V, Hagberg L, Lin A, Nilsson S, Oprea C, Pinnetti C, Spudich S, Trunfio M, Winston A, Price RW, Gisslén M. Cerebrospinal Fluid Viral Load Across the Spectrum of Untreated Human Immunodeficiency Virus Type 1 (HIV-1) Infection: A Cross-Sectional Multicenter Study. Clinical Infectious Diseases 2021, 75: 493-502. PMID: 34747481, PMCID: PMC9427147, DOI: 10.1093/cid/ciab943.Peer-Reviewed Original ResearchConceptsCSF HIV RNAWhite blood cell countPlasma HIV RNAUntreated human immunodeficiency virus type 1 (HIV-1) infectionHuman immunodeficiency virus type 1 (HIV-1) infectionCSF white blood cell countVirus type 1 infectionHIV RNACopies/mLType 1 infectionMulticenter studyOpportunistic central nervous system infectionsCerebrospinal fluid HIV RNACerebrospinal fluid viral loadHigher CSF HIV RNALog10 copies/mLCentral nervous system infectionCross-sectional multicenter studyHIV RNA quantificationNervous system infectionTreatment-naive adultsBlood cell countLarge multicenter studyCNS compartmentalizationCSF discordance
2020
Minimal detection of cerebrospinal fluid escape after initiation of antiretroviral therapy in acute HIV-1 infection.
Handoko R, Chan P, Jagodzinski L, Pinyakorn S, Ubolyam S, Phanuphak N, Sacdalan C, Kroon E, Dumrongpisutikul N, Paul R, Valcour V, Ananworanich J, Vasan S, Spudich S. Minimal detection of cerebrospinal fluid escape after initiation of antiretroviral therapy in acute HIV-1 infection. AIDS 2020, 35: 777-782. PMID: 33306551, PMCID: PMC7969409, DOI: 10.1097/qad.0000000000002786.Peer-Reviewed Original ResearchMeSH KeywordsAnti-Retroviral AgentsCerebrospinal FluidHIV InfectionsHIV-1HumansProspective StudiesRNA, ViralThailandViral LoadConceptsAcute HIV-1 infectionHIV-1 RNACentral nervous systemCSF escapeAntiretroviral therapyHIV-1 infectionWeek 96Week 24HIV-1CSF HIV-1 RNAInitiation of ARTLong-term neurological outcomePlasma HIV-1 RNAWeeks of ARTProspective cohort studyPersistence of HIVHIV-1 persistenceLevels of CSFYears of treatmentHIV-1 replicationNeurological outcomeCohort studyVoluntary counselingChronic infectionEarly treatment
2019
Defining cerebrospinal fluid HIV RNA escape: editorial review AIDS.
Winston A, Antinori A, Cinque P, Fox HS, Gisslen M, Henrich TJ, Letendre S, Persaud D, Price RW, Spudich S. Defining cerebrospinal fluid HIV RNA escape: editorial review AIDS. AIDS 2019, 33 Suppl 2: s107-s111. PMID: 31790376, DOI: 10.1097/qad.0000000000002252.Peer-Reviewed Original Research
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 cellsSingle-cell RNA sequencing reveals microglia-like cells in cerebrospinal fluid during virologically suppressed HIV
Farhadian SF, Mehta SS, Zografou C, Robertson K, Price RW, Pappalardo J, Chiarella J, Hafler DA, Spudich SS. Single-cell RNA sequencing reveals microglia-like cells in cerebrospinal fluid during virologically suppressed HIV. JCI Insight 2018, 3: e121718. PMID: 30232286, PMCID: PMC6237230, DOI: 10.1172/jci.insight.121718.Peer-Reviewed Original ResearchConceptsCerebrospinal fluidHIV infectionImmune activationAntiretroviral therapyNeuronal injuryCentral nervous system immune activationLong-term suppressive antiretroviral therapySingle-cell RNA sequencingCNS immune activationDisease-associated microgliaSuppressive antiretroviral therapyImmune cell subsetsMicroglia-like cellsGene expression signaturesNeuronal damageNeuroinflammatory diseasesRNA sequencingCell subsetsCNS cellsNeurological conditionsRare subsetNeurocognitive impairmentMyeloid cellsCellular subsetsInfection
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 ResearchMeSH KeywordsCD8-Positive T-LymphocytesCerebrospinal FluidHIV AntigensHIV InfectionsHumansImmunophenotypingT-Lymphocyte SubsetsConceptsAcute 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 epitopesImmediate initiation of cART is associated with lower levels of cerebrospinal fluid YKL-40, a marker of microglial activation, in HIV-1 infection
Peluso MJ, Valcour V, Phanuphak N, Ananworanich J, Fletcher JL, Chalermchai T, Krebs SJ, Robb ML, Hellmuth J, Gisslén M, Zetterberg H, Spudich S. Immediate initiation of cART is associated with lower levels of cerebrospinal fluid YKL-40, a marker of microglial activation, in HIV-1 infection. AIDS 2017, 31: 247-252. PMID: 27819802, PMCID: PMC5844231, DOI: 10.1097/qad.0000000000001314.Peer-Reviewed Original ResearchConceptsChronic HIV-1 infectionCombination antiretroviral therapyCerebrospinal fluid (CSF) YKL-40Group of HIVHIV-1 infectionYKL-40Treatment initiationUntreated chronic HIV-1 infectionMedian YKL-40Early HIV infectionCSF YKL-40Chemokine ligand 10Neurofilament light chainCross-sectional studyMann-Whitney testAntiretroviral therapyHIV neuropathogenesisMicroglial activationHIV infectionPrognostic valueChi groupMicroglial cellsAHI groupImmediate initiationBlood sampling
2016
Immune activation in the central nervous system throughout the course of HIV infection
Spudich SS. Immune activation in the central nervous system throughout the course of HIV infection. Current Opinion In HIV And AIDS 2016, 11: 226-233. PMID: 26760827, PMCID: PMC4773903, DOI: 10.1097/coh.0000000000000243.Peer-Reviewed Original ResearchConceptsCombination antiretroviral therapyImmune activationAntiretroviral therapySuppressive combination antiretroviral therapyLong-term neurologic sequelaeCentral nervous system responseCNS immune activationFeatures of homeostasisPersistent immune activationBrain microglial cellsCervical lymph nodesCentral nervous systemSustained immune responseNervous system responsesImmune surveillance networkNeurologic sequelaeAcute infectionHIV infectionLymph nodesActivation associatesMicroglial cellsChronic infectionCNS cellsImmune responseCerebrospinal fluid
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 ResearchMeSH KeywordsAdultCase-Control StudiesCerebrospinal FluidFemaleHIV InfectionsHIV-1HumansMaleMiddle AgedConceptsT 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 systemCD8Cerebrospinal Fluid and Neuroimaging Biomarker Abnormalities Suggest Early Neurological Injury in a Subset of Individuals During Primary HIV Infection
Peluso MJ, Meyerhoff DJ, Price RW, Peterson J, Lee E, Young AC, Walter R, Fuchs D, Brew BJ, Cinque P, Robertson K, Hagberg L, Zetterberg H, Gisslén M, Spudich S. Cerebrospinal Fluid and Neuroimaging Biomarker Abnormalities Suggest Early Neurological Injury in a Subset of Individuals During Primary HIV Infection. The Journal Of Infectious Diseases 2013, 207: 1703-1712. PMID: 23460748, PMCID: PMC3636785, DOI: 10.1093/infdis/jit088.Peer-Reviewed Original ResearchConceptsPrimary HIV infectionNeurofilament light chainHIV infectionAmyloid precursor proteinCerebrospinal fluidNeuronal injuryT-tauCSF/plasma albumin ratioPrimary human immunodeficiency virus (HIV) infectionCentral nervous system inflammationHuman immunodeficiency virus (HIV) infectionSoluble amyloid precursor proteinGamma-induced protein 10Primary infection groupNervous system inflammationImmunodeficiency virus infectionEarly neuronal injuryPlasma albumin ratioParietal gray matterGlutamate/creatineLight chainPrecursor proteinProton magnetic resonance spectroscopyFrontal white matterWhite blood cells
2011
HIV-1 Replication in the Central Nervous System Occurs in Two Distinct Cell Types
Schnell G, Joseph S, Spudich S, Price RW, Swanstrom R. HIV-1 Replication in the Central Nervous System Occurs in Two Distinct Cell Types. PLOS Pathogens 2011, 7: e1002286. PMID: 22007152, PMCID: PMC3188520, DOI: 10.1371/journal.ppat.1002286.Peer-Reviewed Original ResearchConceptsHIV-1-associated dementiaCentral nervous systemHIV-1 populationsMacrophage-tropic virusesCerebrospinal fluidHuman immunodeficiency virus type 1 (HIV-1) infectionNervous systemCSF of subjectsT cell-tropic virusesViral replicationVirus type 1 infectionType 1 infectionHIV-1 replicationHIV-1 variantsHAD subjectsCNS infectionsTherapy initiationCCR5-tropicOvert dementiaVirological characteristicsNeurocognitive disordersHIV-1Virological stateSurface CD4CSF compartment
2010
HIV-1 Viral Escape in Cerebrospinal Fluid of Subjects on Suppressive Antiretroviral Treatment
Edén A, Fuchs D, Hagberg L, Nilsson S, Spudich S, Svennerholm B, Price RW, Gisslén M. HIV-1 Viral Escape in Cerebrospinal Fluid of Subjects on Suppressive Antiretroviral Treatment. The Journal Of Infectious Diseases 2010, 202: 1819-1825. PMID: 21050119, PMCID: PMC3052942, DOI: 10.1086/657342.Peer-Reviewed Original ResearchConceptsHIV-1 RNAAntiretroviral therapy regimensCerebrospinal fluidViral escapeTherapy regimensPlasma human immunodeficiency virus type 1 (HIV-1) RNACSF HIV-1 RNAHuman immunodeficiency virus type 1 (HIV-1) RNACentral nervous system infectionCSF neopterin levelsCSF viral escapeHigher CSF neopterinIntrathecal immune activationPrevious treatment interruptionsSuppressive antiretroviral treatmentAtazanavir/ritonavirLopinavir/ritonavirNervous system infectionCSF virusNew treatment combinationsCopies/mLEnzyme-linked immunosorbentPolymerase chain reaction assaysCSF escapeCSF neopterin
2009
Compartmentalized Human Immunodeficiency Virus Type 1 Originates from Long-Lived Cells in Some Subjects with HIV-1–Associated Dementia
Schnell G, Spudich S, Harrington P, Price RW, Swanstrom R. Compartmentalized Human Immunodeficiency Virus Type 1 Originates from Long-Lived Cells in Some Subjects with HIV-1–Associated Dementia. PLOS Pathogens 2009, 5: e1000395. PMID: 19390619, PMCID: PMC2668697, DOI: 10.1371/journal.ppat.1000395.Peer-Reviewed Original ResearchConceptsHIV-1-associated dementiaCentral nervous systemAntiretroviral therapyCerebrospinal fluidNeurological diseasesAsymptomatic subjectsHIV-1-associated neurological diseasePeripheral CD4 cell countViral replicationHuman immunodeficiency virus type 1HIV-1 associated dementiaViral decayImmunodeficiency virus type 1HIV-1 genetic variantsCNS drug penetrationRapid viral decayViral decay kineticsCD4 cell countDrug-resistant virusesHigh viral loadHIV-1 variantsVirus type 1Productive viral replicationHAD subjectsCSF pleocytosis
2008
Antiretroviral Treatment Effect on Immune Activation Reduces Cerebrospinal Fluid HIV-1 Infection
Sinclair E, Ronquillo R, Lollo N, Deeks SG, Hunt P, Yiannoutsos CT, Spudich S, Price RW. Antiretroviral Treatment Effect on Immune Activation Reduces Cerebrospinal Fluid HIV-1 Infection. JAIDS Journal Of Acquired Immune Deficiency Syndromes 2008, 47: 544-552. PMID: 18362693, PMCID: PMC3480328, DOI: 10.1097/qai.0b013e318162754f.Peer-Reviewed Original ResearchConceptsPlasma HIV-1 RNACD8 T cell activationHIV-1 RNACSF HIV-1 RNA levelsHIV-1 RNA levelsT cell activationWhite blood cellsHIV-1 concentrationsAntiretroviral therapyHIV-1 infectionCerebrospinal fluidCD8 activationCSF neopterinViremic groupImmune activationCopies/HIV-1CD38/HLA-DR expressionCSF HIV-1 RNA concentrationsHIV-1-infected subjectsSystemic HIV-1 infectionHIV-1 RNA concentrationsHuman leukocyte antigen-DRCSF white blood cellsCoexpression of CD38Persistent Intrathecal Immune Activation in HIV-1-Infected Individuals on Antiretroviral Therapy
Yilmaz A, Price RW, Spudich S, Fuchs D, Hagberg L, Gisslén M. Persistent Intrathecal Immune Activation in HIV-1-Infected Individuals on Antiretroviral Therapy. JAIDS Journal Of Acquired Immune Deficiency Syndromes 2008, 47: 168-173. PMID: 17971711, PMCID: PMC2628632, DOI: 10.1097/qai.0b013e31815ace97.Peer-Reviewed Original ResearchConceptsCSF neopterin levelsHIV-1-infected patientsHIV-1-infected individualsCSF neopterin concentrationsCSF viral loadIntrathecal immune activationAntiretroviral therapyHIV-1 RNACopies/mLNeopterin levelsViral loadNeopterin concentrationsImmune activationCSF HIV-1 RNA loadMost HIV-1-infected individualsPlasma HIV-1 RNA levelsCerebrospinal fluid (CSF) neopterin levelsQuantitative HIV-1 RNAHIV-1 RNA levelsHIV-1 RNA loadCell-mediated immune responsesHIV-1 RNA quantificationHIV-1 concentrationsStable antiretroviral therapySuppressive antiretroviral therapy
2005
HIV-1 Chemokine Coreceptor Utilization in Paired Cerebrospinal Fluid and Plasma Samples: A Survey of Subjects with Viremia
Spudich SS, Huang W, Nilsson AC, Petropoulos CJ, Liegler TJ, Whitcomb JM, Price RW. HIV-1 Chemokine Coreceptor Utilization in Paired Cerebrospinal Fluid and Plasma Samples: A Survey of Subjects with Viremia. The Journal Of Infectious Diseases 2005, 191: 890-898. PMID: 15717264, DOI: 10.1086/428095.Peer-Reviewed Original ResearchConceptsCerebrospinal fluidImmunodeficiency syndrome dementia complexCD4 T-cell countHuman immunodeficiency virus type 1 (HIV-1) entryMixture of R5Paired Cerebrospinal FluidT-cell countsPlasma samplesSurvey of subjectsHIV-1 populationsAdvanced immunodeficiencyCoreceptor utilizationInhibitor therapyPrincipal coreceptorR5 phenotypeX4 virusesDementia complexR5 virusesR5 tropismChemokine receptorsInfection pathogenesisCell countViral tropismDiscordant tropismCell tropism