Featured Publications
Retroviruses use CD169-mediated trans-infection of permissive lymphocytes to establish infection
Sewald X, Ladinsky MS, Uchil PD, Beloor J, Pi R, Herrmann C, Motamedi N, Murooka TT, Brehm MA, Greiner DL, Shultz LD, Mempel TR, Bjorkman PJ, Kumar P, Mothes W. Retroviruses use CD169-mediated trans-infection of permissive lymphocytes to establish infection. Science 2015, 350: 563-567. PMID: 26429886, PMCID: PMC4651917, DOI: 10.1126/science.aab2749.Peer-Reviewed Original ResearchConceptsHuman immunodeficiency virusLymph nodesMurine leukemia virusCD169/SiglecSecondary lymphoid tissuesPermissive lymphocytesDendritic cellsImmunodeficiency virusSynaptic contactsLymphoid tissueRobust infectionVirological synapsesI-type lectinsRetroviral spreadViral spreadUninfected cellsInfectionLeukemia virusVirusMacrophagesCellsRetrovirusesCell-cell contactCD169LymphocytesTRIM5 is an innate immune sensor for the retrovirus capsid lattice
Pertel T, Hausmann S, Morger D, Züger S, Guerra J, Lascano J, Reinhard C, Santoni FA, Uchil PD, Chatel L, Bisiaux A, Albert ML, Strambio-De-Castillia C, Mothes W, Pizzato M, Grütter MG, Luban J. TRIM5 is an innate immune sensor for the retrovirus capsid lattice. Nature 2011, 472: 361-365. PMID: 21512573, PMCID: PMC3081621, DOI: 10.1038/nature09976.Peer-Reviewed Original ResearchMeSH KeywordsAntiviral Restriction FactorsCapsidCarrier ProteinsCell LineEnzyme ActivationHEK293 CellsHIV-1HumansImmunity, InnateLipopolysaccharidesMAP Kinase Kinase KinasesNF-kappa BProtein BindingReceptors, Pattern RecognitionRetroviridaeSignal TransductionTranscription Factor AP-1Transcription FactorsTripartite Motif ProteinsUbiquitinUbiquitin-Conjugating EnzymesUbiquitin-Protein Ligases
2023
HIV-1 Env trimers asymmetrically engage CD4 receptors in membranes
Li W, Qin Z, Nand E, Grunst M, Grover J, Bess J, Lifson J, Zwick M, Tagare H, Uchil P, Mothes W. HIV-1 Env trimers asymmetrically engage CD4 receptors in membranes. Nature 2023, 623: 1026-1033. PMID: 37993716, PMCID: PMC10686830, DOI: 10.1038/s41586-023-06762-6.Peer-Reviewed Original ResearchConceptsHIV-1 Env trimersCD4 moleculeHuman immunodeficiency virus-1 (HIV-1) infectionEnv trimersAntibody-mediated immune responsesEnv-CD4 interactionVirus-1 infectionVaccine immunogen designViral envelope glycoproteinsHIV-1Immune responseCD4 receptorImmunogen designEnvelope glycoproteinVirus-like particlesCD4EnvHost cell membraneAntiviral HIV-1 SERINC restriction factors disrupt virus membrane asymmetry
Leonhardt S, Purdy M, Grover J, Yang Z, Poulos S, McIntire W, Tatham E, Erramilli S, Nosol K, Lai K, Ding S, Lu M, Uchil P, Finzi A, Rein A, Kossiakoff A, Mothes W, Yeager M. Antiviral HIV-1 SERINC restriction factors disrupt virus membrane asymmetry. Nature Communications 2023, 14: 4368. PMID: 37474505, PMCID: PMC10359404, DOI: 10.1038/s41467-023-39262-2.Peer-Reviewed Original Research
2019
Longitudinal bioluminescent imaging of HIV-1 infection during antiretroviral therapy and treatment interruption in humanized mice
Ventura JD, Beloor J, Allen E, Zhang T, Haugh KA, Uchil PD, Ochsenbauer C, Kieffer C, Kumar P, Hope TJ, Mothes W. Longitudinal bioluminescent imaging of HIV-1 infection during antiretroviral therapy and treatment interruption in humanized mice. PLOS Pathogens 2019, 15: e1008161. PMID: 31805155, PMCID: PMC6917343, DOI: 10.1371/journal.ppat.1008161.Peer-Reviewed Original ResearchConceptsHIV-1 infectionHumanized miceCombination antiretroviral therapy regimenViral spreadHIV-1 infection dynamicsNon-invasive bioluminescentAntiretroviral therapy regimenHIV-1 reporterSame lymphoid tissuesInfected cell populationCART withdrawalInfection recrudescenceAntiretroviral therapyTreatment interruptionTherapy regimenLymphoid tissueInfection dynamicsART treatmentBioluminescent imagingInfectionViral infection dynamicsInfected cellsCell populationsMiceBioluminescent signal
2015
HIV cell-to-cell transmission: effects on pathogenesis and antiretroviral therapy
Agosto LM, Uchil PD, Mothes W. HIV cell-to-cell transmission: effects on pathogenesis and antiretroviral therapy. Trends In Microbiology 2015, 23: 289-295. PMID: 25766144, PMCID: PMC4417442, DOI: 10.1016/j.tim.2015.02.003.Peer-Reviewed Original ResearchConceptsAntiretroviral therapyVirological synapsesT-cell depletionCell transmissionHIV infectionCell depletionHIV cellMatter of debateViral replicationTherapyUninfected cellsReduced efficacyHigh MOISynapsesHIVPathogenesisRecent dataInfectionCell deathTrigger cell deathCellsVivoCell-cell contactCellular surveillanceHigher number
2012
TRIM Protein-Mediated Regulation of Inflammatory and Innate Immune Signaling and Its Association with Antiretroviral Activity
Uchil PD, Hinz A, Siegel S, Coenen-Stass A, Pertel T, Luban J, Mothes W. TRIM Protein-Mediated Regulation of Inflammatory and Innate Immune Signaling and Its Association with Antiretroviral Activity. Journal Of Virology 2012, 87: 257-272. PMID: 23077300, PMCID: PMC3536418, DOI: 10.1128/jvi.01804-12.Peer-Reviewed Original ResearchConceptsInnate immune signalingNF-κBMurine leukemia virusImmune signalingInterferon productionAP-1Human immunodeficiency virus type 1 (HIV-1) gene expressionNF-κB/APHIV-1 resistanceVesicular stomatitis virus replicationTRIM proteinsLipopolysaccharide challengeAntiretroviral activityHIV-1NF-κB siteInnate immunityViral replicationVirus replicationPrimary macrophagesLeukemia virusCritical regulatorPathway upstreamSignalingKnockdownGene expression
2011
Targeted Disruption of the CCR5 Gene in Human Hematopoietic Stem Cells Stimulated by Peptide Nucleic Acids
Schleifman EB, Bindra R, Leif J, del Campo J, Rogers FA, Uchil P, Kutsch O, Shultz LD, Kumar P, Greiner DL, Glazer PM. Targeted Disruption of the CCR5 Gene in Human Hematopoietic Stem Cells Stimulated by Peptide Nucleic Acids. Cell Chemical Biology 2011, 18: 1189-1198. PMID: 21944757, PMCID: PMC3183429, DOI: 10.1016/j.chembiol.2011.07.010.Peer-Reviewed Original ResearchConceptsHematopoietic stem cellsHIV-1CCR5 geneHIV-1-infected individualsHIV-1 infectionGene modificationHIV-1 entryCCR5-Delta32 mutationImmune system functionStem cellsCCR5 knockoutMonths posttransplantationChemokine receptorsHuman hematopoietic stem cellsTherapeutic strategiesSubsequent engraftmentGenome modificationProtein levelsHuman cellsTargeted disruptionCCR5Peptide nucleic acidInfectionNucleic acidsCellsTRIM22 Inhibits HIV-1 Transcription Independently of Its E3 Ubiquitin Ligase Activity, Tat, and NF-κB-Responsive Long Terminal Repeat Elements
Kajaste-Rudnitski A, Marelli SS, Pultrone C, Pertel T, Uchil PD, Mechti N, Mothes W, Poli G, Luban J, Vicenzi E. TRIM22 Inhibits HIV-1 Transcription Independently of Its E3 Ubiquitin Ligase Activity, Tat, and NF-κB-Responsive Long Terminal Repeat Elements. Journal Of Virology 2011, 85: 5183-5196. PMID: 21345949, PMCID: PMC3126207, DOI: 10.1128/jvi.02302-10.Peer-Reviewed Original ResearchConceptsHIV-1 replicationHIV-1 transcriptionHuman immunodeficiency virus type 1 (HIV-1) replicationU937 promonocytic cell lineHIV-1 restriction factorsTumor necrosis factor alphaInhibits HIV-1 transcriptionType 1 replicationRestriction factorsHIV-1 productionNecrosis factor alphaLower peak levelsPermissive cellsHIV-1 LTRHost restriction factorsPromonocytic cell lineU937 cellsReplication-competent virusNF-κB binding siteFactor alphaT cellsHIV-1Overexpression of TRIM22NF-κBLTR transactivation
2008
Retroviruses Human Immunodeficiency Virus and Murine Leukemia Virus Are Enriched in Phosphoinositides
Chan R, Uchil PD, Jin J, Shui G, Ott DE, Mothes W, Wenk MR. Retroviruses Human Immunodeficiency Virus and Murine Leukemia Virus Are Enriched in Phosphoinositides. Journal Of Virology 2008, 82: 11228-11238. PMID: 18799574, PMCID: PMC2573248, DOI: 10.1128/jvi.00981-08.Peer-Reviewed Original ResearchConceptsPlasma membraneMurine leukemia virusHIV-1 buddingLipid contentLeukemia virusMass spectrometry analysisCholesterol-rich regionsOverall lipid contentCell peripheryMutant virionsLipid envelopeTotal lipid contentPhosphorylated derivativesSpectrometry analysisPhosphoinositideRetrovirusesMembraneCellsMatrix domainParticle releaseHuman immunodeficiency virus type 1Immunodeficiency virus type 1VirusVirus type 1PhosphatidylinositolEffective suppression of HIV-1 by artificial bispecific miRNA targeting conserved sequences with tolerance for wobble base-pairing
Son J, Uchil PD, Kim YB, Shankar P, Kumar P, Lee SK. Effective suppression of HIV-1 by artificial bispecific miRNA targeting conserved sequences with tolerance for wobble base-pairing. Biochemical And Biophysical Research Communications 2008, 374: 214-218. PMID: 18619945, DOI: 10.1016/j.bbrc.2008.06.125.Peer-Reviewed Original ResearchConceptsFunctional RNAiHIV-1 isolatesHigh genetic diversityAntiviral therapyHIV replicationHIV-1Vif sequencesArtificial microRNAsGenetic diversityGenome sequenceSustained inhibitionVif geneHIV sequencesVariant residuesSequence databasesLuciferase constructSimultaneous targetingNatural variantsViral sequencesRNAiSequenceInhibition