2022
Single-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 expressionCD4
2020
Single-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
2013
Single-copy assay quantification of HIV-1 RNA in paired cerebrospinal fluid and plasma samples from elite controllers
Dahl V, Peterson J, Spudich S, Lee E, Shacklett BL, Price RW, Palmer S. Single-copy assay quantification of HIV-1 RNA in paired cerebrospinal fluid and plasma samples from elite controllers. AIDS 2013, 27: 1145-1149. PMID: 23211774, PMCID: PMC4004626, DOI: 10.1097/qad.0b013e32835cf235.Peer-Reviewed Original ResearchConceptsHIV-1 RNACentral nervous systemHIV-1 RNA quantificationElite controllersCerebrospinal fluidPlasma samplesCSF samplesHIV-1 RNA concentrationsHIV-1-infected individualsConcurrent plasma samplesSingle-copy assayRNA quantificationAntiretroviral therapyCopies/HIV-1Rare subsetNervous systemRNA concentrationClinical assaysSensitive assayAssaysRNATherapyInfectionBlood
2009
Compartmentalization and Clonal Amplification of HIV-1 Variants in the Cerebrospinal Fluid during Primary Infection
Schnell G, Price RW, Swanstrom R, Spudich S. Compartmentalization and Clonal Amplification of HIV-1 Variants in the Cerebrospinal Fluid during Primary Infection. Journal Of Virology 2009, 84: 2395-2407. PMID: 20015984, PMCID: PMC2820937, DOI: 10.1128/jvi.01863-09.Peer-Reviewed Original ResearchConceptsHIV-1 populationsPrimary HIV-1 infectionCentral nervous systemHIV-1 infectionHIV-1 variantsDistinct HIV-1 populationsIndependent HIV-1 replicationHIV-1-infected individualsHuman immunodeficiency virus type 1Full-length env genesImmunodeficiency virus type 1HIV-1 transmissionSingle genome amplificationHIV-1 replicationHeteroduplex tracking assaysCourse of infectionSubset of subjectsVirus type 1Severe neurological diseaseClonal amplificationPeripheral bloodPrimary infectionCNS environmentCerebrospinal fluidNervous systemRaltegravir Cerebrospinal Fluid Concentrations in HIV-1 Infection
Yilmaz A, Gisslén M, Spudich S, Lee E, Jayewardene A, Aweeka F, Price RW. Raltegravir Cerebrospinal Fluid Concentrations in HIV-1 Infection. PLOS ONE 2009, 4: e6877. PMID: 19721718, PMCID: PMC2731205, DOI: 10.1371/journal.pone.0006877.Peer-Reviewed Original ResearchConceptsHIV-1 infectionRaltegravir concentrationsCerebrospinal fluidTreatment-experienced HIV-1-infected patientsSystemic HIV-1 infectionHIV-1-infected patientsHIV-1-infected individualsIntegrase inhibitorsCentral nervous system penetrationAntiretroviral treatment regimensDrug entryPlasma albumin ratioCerebrospinal fluid concentrationsBlood-CSF barrierCSF albumin concentrationPlasma raltegravir concentrationsTreatment regimensAlbumin ratioDrug classesCSF specimensHIV-1CSF samplesAlbumin concentrationFluid concentrationsLiquid chromatography-tandem mass spectrometry
2008
Enfuvirtide Cerebrospinal Fluid (CSF) Pharmacokinetics and Potential use in Defining CSF HIV-1 Origin
Price RW, Parham R, Kroll JL, Wring SA, Baker B, Sailstad J, Hoh R, Liegler T, Spudich S, Kuritzkes DR, Deeks SG. Enfuvirtide Cerebrospinal Fluid (CSF) Pharmacokinetics and Potential use in Defining CSF HIV-1 Origin. Antiviral Therapy 2008, 13: 369-374. PMID: 18572749, PMCID: PMC2699482, DOI: 10.1177/135965350801300312.Peer-Reviewed Original ResearchConceptsCentral nervous systemCerebrospinal fluidCSF samplesCSF HIV-1 RNAHIV-1-infected individualsHIV-negative individualsCerebrospinal fluid pharmacokineticsHIV-1 RNAHuman central nervous systemPlasma samplesHIV-1 replicationCNS drug exposureHIV-1 quasispeciesUse of enfuvirtideResistance-associated mutationsLocal therapeutic effectCNS virusV38A mutationGp41 coding regionCSF pharmacokineticsDrug exposurePlasma concentrationsTherapeutic effectNervous systemClinical settingPersistent 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