Pradeep Uchil, PhD
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Architecture of the Flaviviral Replication Complex PROTEASE, NUCLEASE, AND DETERGENTS REVEAL ENCASEMENT WITHIN DOUBLE-LAYERED MEMBRANE COMPARTMENTS*
Uchil P, Satchidanandam V. Architecture of the Flaviviral Replication Complex PROTEASE, NUCLEASE, AND DETERGENTS REVEAL ENCASEMENT WITHIN DOUBLE-LAYERED MEMBRANE COMPARTMENTS*. Journal Of Biological Chemistry 2003, 278: 24388-24398. PMID: 12700232, DOI: 10.1074/jbc.m301717200.Peer-Reviewed Original ResearchConceptsViral genomic RNAVesicle packetsMembrane compartmentsGenomic RNADouble-membrane compartmentsInner membrane vesiclesViral RNA speciesHost cell membraneHeavy membrane fractionNonionic detergent extractsRNA speciesReplicative intermediate RNAViral NS3Replication complexPrior trypsin treatmentMicrococcal nucleaseComplex proteaseMembranous sitesReplicative form RNASpecialized structuresActive proteinIntermediate RNAMembrane vesiclesMembrane fractionForm RNAPhylogenetic analysis of Japanese encephalitis virus: envelope gene based analysis reveals a fifth genotype, geographic clustering, and multiple introductions of the virus into the Indian subcontinent.
Uchil P, Satchidanandam V. Phylogenetic analysis of Japanese encephalitis virus: envelope gene based analysis reveals a fifth genotype, geographic clustering, and multiple introductions of the virus into the Indian subcontinent. American Journal Of Tropical Medicine And Hygiene 2001, 65: 242-51. PMID: 11561712, DOI: 10.4269/ajtmh.2001.65.242.Peer-Reviewed Original ResearchMeSH KeywordsAedesAmino Acid SequenceAnimalsBase SequenceCell LineCluster AnalysisDNA, ComplementaryEncephalitis Virus, JapaneseEncephalitis, JapaneseEvolution, MolecularGenes, envGenetic VariationGenotypeHumansIndiaMolecular Sequence DataPhylogenyReverse Transcriptase Polymerase Chain ReactionRNA, ViralSequence Homology, Amino AcidSequence Homology, Nucleic AcidSwineThe Fc-effector function of COVID-19 convalescent plasma contributes to SARS-CoV-2 treatment efficacy in mice
Ullah I, Beaudoin-Bussières G, Symmes K, Cloutier M, Ducas E, Tauzin A, Laumaea A, Grunst M, Dionne K, Richard J, Bégin P, Mothes W, Kumar P, Bazin R, Finzi A, Uchil P. The Fc-effector function of COVID-19 convalescent plasma contributes to SARS-CoV-2 treatment efficacy in mice. Cell Reports Medicine 2022, 4: 100893. PMID: 36584683, PMCID: PMC9799175, DOI: 10.1016/j.xcrm.2022.100893.Peer-Reviewed Original ResearchConceptsCOVID-19 convalescent plasmaFc effector functionsSARS-CoV-2 controlFc effector activityInnate immune cellsCCP efficacyHACE2 miceConvalescent plasmaImmunoglobulin levelsPlasma therapyImmune cellsTreatment efficacyDelays mortalityIgG fractionFc functionLow neutralizingTherapySecond lineMortalityMicePlasma contributesEfficacyFC activityProphylaxisIgGIn vivo imaging of retrovirus infection reveals a role for Siglec-1/CD169 in multiple routes of transmission
Haugh KA, Ladinsky MS, Ullah I, Stone HM, Pi R, Gilardet A, Grunst MW, Kumar P, Bjorkman PJ, Mothes W, Uchil PD. In vivo imaging of retrovirus infection reveals a role for Siglec-1/CD169 in multiple routes of transmission. ELife 2021, 10: e64179. PMID: 34223819, PMCID: PMC8298093, DOI: 10.7554/elife.64179.Peer-Reviewed Original ResearchConceptsSentinel macrophagesSiglec-1/CD169Immune surveillance functionCommon host factorMesenteric sacsPeyer's patchesGastrointestinal tractOral routeReporter virusRetrovirus transmissionRetrovirus infectionFrontline cellsRetroviral pathogenesisHost factorsBioluminescence imagingVirus entryIncoming virusInfectionRetrovirus life cycleCD169Early eventsMacrophagesMultiscale imaging approachVirusSurveillance functionLive imaging of SARS-CoV-2 infection in mice reveals that neutralizing antibodies require Fc function for optimal efficacy
Ullah I, Prévost J, Ladinsky MS, Stone H, Lu M, Anand SP, Beaudoin-Bussières G, Symmes K, Benlarbi M, Ding S, Gasser R, Fink C, Chen Y, Tauzin A, Goyette G, Bourassa C, Medjahed H, Mack M, Chung K, Wilen CB, Dekaban GA, Dikeakos JD, Bruce EA, Kaufmann DE, Stamatatos L, McGuire AT, Richard J, Pazgier M, Bjorkman PJ, Mothes W, Finzi A, Kumar P, Uchil PD. Live imaging of SARS-CoV-2 infection in mice reveals that neutralizing antibodies require Fc function for optimal efficacy. Immunity 2021, 54: 2143-2158.e15. PMID: 34453881, PMCID: PMC8372518, DOI: 10.1016/j.immuni.2021.08.015.Peer-Reviewed Original ResearchConceptsCOVID-19 convalescent subjectsSARS-CoV-2 infectionBioluminescence imagingK18-hACE2 miceLive bioluminescence imagingNatural killer cellsFc effector functionsSARS-CoV-2Convalescent subjectsKiller cellsPotent NAbsImmune protectionInflammatory responseEffector functionsNasal cavityNaB treatmentOptimal efficacyFc functionDepletion studiesMiceNAbsCOVID-19Direct neutralizationInfectionAntibodiesA Protective Role for the Lectin CD169/Siglec-1 against a Pathogenic Murine Retrovirus
Uchil PD, Pi R, Haugh KA, Ladinsky MS, Ventura JD, Barrett BS, Santiago ML, Bjorkman PJ, Kassiotis G, Sewald X, Mothes W. A Protective Role for the Lectin CD169/Siglec-1 against a Pathogenic Murine Retrovirus. Cell Host & Microbe 2018, 25: 87-100.e10. PMID: 30595553, PMCID: PMC6331384, DOI: 10.1016/j.chom.2018.11.011.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD8-Positive T-LymphocytesCell ProliferationDendritic CellsDisease Models, AnimalErythroblastsFemaleInterferon Type ILectinsLymph NodesMacrophagesMaleMiceMice, Inbred BALB CMice, Inbred C57BLProtective AgentsRetroviridaeRetroviridae InfectionsSialic Acid Binding Ig-like Lectin 1SpleenT-Lymphocytes, CytotoxicViral LoadConceptsCD169/SiglecEffective cytotoxic T lymphocyte (CTL) responseProtective roleCytotoxic T lymphocyte responsesLymph node infectionT lymphocyte responsesHigh viral loadSusceptible mouse strainsMarginal zone metallophilic macrophagesPermissive lymphocytesCytotoxic CD8Lymphocyte responsesViral loadSubcapsular sinusComplex infectionMurine modelViral disseminationMetallophilic macrophagesRed pulpCell responsesSystemic spreadMouse strainsPathogenesisCells 1CD169Retroviruses 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 LigasesTRIM E3 Ligases Interfere with Early and Late Stages of the Retroviral Life Cycle
Uchil PD, Quinlan BD, Chan WT, Luna JM, Mothes W. TRIM E3 Ligases Interfere with Early and Late Stages of the Retroviral Life Cycle. PLOS Pathogens 2008, 4: e16. PMID: 18248090, PMCID: PMC2222954, DOI: 10.1371/journal.ppat.0040016.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnti-Retroviral AgentsApoptosisAvian leukosis virusCell SurvivalGag Gene Products, Human Immunodeficiency VirusGene Expression Regulation, ViralGene SilencingHeLa CellsHIVHost-Pathogen InteractionsHumansLeukemia Virus, MurineMiceRetroviridaeUbiquitin-Protein LigasesVirus ReplicationConceptsHuman immunodeficiency virus-1Viral life cycleMurine leukemia virusAvian leukosis virusImmunodeficiency virus-1Antiretroviral activityHIV entryTRIM proteinsAntiviral activityLater stagesVirus 1TRIM11Virus releaseViral releaseLeukemia virusRetroviral life cycleHEK293 cellsLeukosis virusVirusComprehensive screenReleaseCellsProteinTRIM15 is a focal adhesion protein that regulates focal adhesion disassembly
Uchil PD, Pawliczek T, Reynolds TD, Ding S, Hinz A, Munro JB, Huang F, Floyd RW, Yang H, Hamilton WL, Bewersdorf J, Xiong Y, Calderwood DA, Mothes W. TRIM15 is a focal adhesion protein that regulates focal adhesion disassembly. Journal Of Cell Science 2014, 127: 3928-3942. PMID: 25015296, PMCID: PMC4163643, DOI: 10.1242/jcs.143537.Peer-Reviewed Original ResearchConceptsFocal adhesion proteinsFocal adhesionsCell migrationAdhesion proteinsMulti-adaptor proteinTripartite motif (TRIM) protein familyFocal adhesion dynamicsFocal adhesion turnoverFocal adhesion componentsCoiled-coil domainImpaired cell migrationII-independent mannerLD2 motifAdhesion turnoverActin cytoskeletonProtein familyAdhesion dynamicsCellular functionsDynamic turnoverMacromolecular complexesRegulatory componentsFocal contactsAdhesion componentsExtracellular matrixTRIM15