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 contactCD169Lymphocytes
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 ResearchMeSH KeywordsAntiviral AgentsAntiviral Restriction FactorsHIV InfectionsHIV-1HumansMembrane GlycoproteinsMembrane Proteins
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
2013
Cell-to-Cell Transmission Can Overcome Multiple Donor and Target Cell Barriers Imposed on Cell-Free HIV
Zhong P, Agosto LM, Ilinskaya A, Dorjbal B, Truong R, Derse D, Uchil PD, Heidecker G, Mothes W. Cell-to-Cell Transmission Can Overcome Multiple Donor and Target Cell Barriers Imposed on Cell-Free HIV. PLOS ONE 2013, 8: e53138. PMID: 23308151, PMCID: PMC3538641, DOI: 10.1371/journal.pone.0053138.Peer-Reviewed Original ResearchConceptsCell-free human immunodeficiency virusHuman immunodeficiency virusTarget cell typeCell transmissionTarget T cellsCell-free virusCell-free modeRestriction factor tetherinCell typesViral replication cycleHIV transmissionImmunodeficiency virusHIV cellT cellsTarget cellsDonor cellsVirus transmissionCell barrierPermissive cellsVirusProviral contentMultiple donorsReplication cycleCell contactExtracellular space
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 acidsCells
2009
HIV Entry Revisited
Uchil PD, Mothes W. HIV Entry Revisited. Cell 2009, 137: 402-404. PMID: 19410537, PMCID: PMC2803685, DOI: 10.1016/j.cell.2009.04.033.Peer-Reviewed Original Research