2024
Electron tomography visualization of HIV-1 virions trapped by fusion inhibitors to host cells in infected tissues
Ladinsky M, Zhu L, Ullah I, Uchil P, Kumar P, Kay M, Bjorkman P. Electron tomography visualization of HIV-1 virions trapped by fusion inhibitors to host cells in infected tissues. Journal Of Virology 2024, 98: e01432-24. PMID: 39475277, PMCID: PMC11575291, DOI: 10.1128/jvi.01432-24.Peer-Reviewed Original ResearchHIV-1 virionsHIV-1 target cellsHIV-1Fusion inhibitorsTarget cellsBone marrow/liver/thymus miceHIV-1 pseudovirionsCo-receptorHost cell membraneTZM-bl cellsPre-hairpin intermediateVascular endothelial cellsCell surfaceHumanized miceTZM-blCell membraneInfected tissuesEnvEndothelial cellsViral envelopeBind host receptorsHost receptorsInhibitorsCo-receptor proteinsPresence of virions
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
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
Effective 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