Featured Publications
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 ResearchMeSH KeywordsAnimalsCell LineDetergentsEndopeptidasesFlavivirusRibonucleasesRNA, ViralVirus ReplicationConceptsViral 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 RNATRIM 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 screenReleaseCellsProtein
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 ResearchMeSH KeywordsAnimalsAnti-HIV AgentsDisease Models, AnimalHIV InfectionsHIV-1HumansLuminescent MeasurementsLymphoid TissueMiceVirus ReplicationConceptsHIV-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 signalMurine Leukemia Virus Exploits Innate Sensing by Toll-Like Receptor 7 in B-1 Cells To Establish Infection and Locally Spread in Mice
Pi R, Iwasaki A, Sewald X, Mothes W, Uchil PD. Murine Leukemia Virus Exploits Innate Sensing by Toll-Like Receptor 7 in B-1 Cells To Establish Infection and Locally Spread in Mice. Journal Of Virology 2019, 93: 10.1128/jvi.00930-19. PMID: 31434732, PMCID: PMC6803250, DOI: 10.1128/jvi.00930-19.Peer-Reviewed Original ResearchConceptsPopliteal lymph nodesFriend murine leukemia virusInnate immune sensing pathwaysToll-like receptor 7Viral spreadMurine leukemia virusCell-deficient miceType I interferon responseWild-type miceCell populationsType I interferonLeukemia virusRobust virus replicationI interferon responseAntiviral intervention strategiesInfected cell typesSentinel macrophagesAdoptive transferCell typesLymph nodesReceptor 7Virus infectionInnate sensingB cellsI interferonIn vivo Imaging-Driven Approaches to Study Virus Dissemination and Pathogenesis
Uchil PD, Haugh KA, Pi R, Mothes W. In vivo Imaging-Driven Approaches to Study Virus Dissemination and Pathogenesis. Annual Review Of Virology 2019, 6: 1-24. PMID: 31283440, PMCID: PMC7217087, DOI: 10.1146/annurev-virology-101416-041429.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDiagnostic ImagingDisease Models, AnimalHumansVirus DiseasesVirus Physiological PhenomenaVirus ReplicationViruses
2018
Small Interfering RNA-Mediated Control of Virus Replication in the CNS Is Therapeutic and Enables Natural Immunity to West Nile Virus
Beloor J, Maes N, Ullah I, Uchil P, Jackson A, Fikrig E, Lee SK, Kumar P. Small Interfering RNA-Mediated Control of Virus Replication in the CNS Is Therapeutic and Enables Natural Immunity to West Nile Virus. Cell Host & Microbe 2018, 23: 549-556.e3. PMID: 29606496, PMCID: PMC6074029, DOI: 10.1016/j.chom.2018.03.001.Peer-Reviewed Original ResearchConceptsWest Nile virusWNV infectionCell-mediated immune responsesLate-stage therapySubsequent WNV infectionWNV-infected miceLong-term immunityNile virusWNV E proteinViral burdenIntranasal routeVirus clearanceVirus infectionImmune responseMice succumbPeripheral tissuesNatural immunitySurvival rateDisease resultsDay 9Virus replicationInfectionImmunityCNSVirus
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
2011
TRIM22 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
RNA interference screen for human genes associated with West Nile virus infection
Krishnan MN, Ng A, Sukumaran B, Gilfoy FD, Uchil PD, Sultana H, Brass AL, Adametz R, Tsui M, Qian F, Montgomery RR, Lev S, Mason PW, Koski RA, Elledge SJ, Xavier RJ, Agaisse H, Fikrig E. RNA interference screen for human genes associated with West Nile virus infection. Nature 2008, 455: 242-245. PMID: 18690214, PMCID: PMC3136529, DOI: 10.1038/nature07207.Peer-Reviewed Original ResearchMeSH KeywordsComputational BiologyDengue VirusEndoplasmic ReticulumGene Expression ProfilingGenome, HumanHeLa CellsHIVHumansImmunityMonocarboxylic Acid TransportersMuscle ProteinsProtein BindingRNA InterferenceUbiquitinationUbiquitin-Protein LigasesVesiculovirusVirus ReplicationWest Nile FeverWest Nile virusEffective 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
2006
Organization of Flaviviral Replicase Proteins in Virus‐Induced Membranes: a Role for NS1′ in Japanese Encephalitis Virus RNA Synthesis
Satchidanandam V, Uchil PD, Kumar P. Organization of Flaviviral Replicase Proteins in Virus‐Induced Membranes: a Role for NS1′ in Japanese Encephalitis Virus RNA Synthesis. Novartis Foundation Symposia 2006, 277: 136-148. PMID: 17319159, DOI: 10.1002/0470058005.ch10.Peer-Reviewed Original ResearchNuclear Localization of Flavivirus RNA Synthesis in Infected Cells
Uchil P, Kumar A, Satchidanandam V. Nuclear Localization of Flavivirus RNA Synthesis in Infected Cells. Journal Of Virology 2006, 80: 5451-5464. PMID: 16699025, PMCID: PMC1472159, DOI: 10.1128/jvi.01982-05.Peer-Reviewed Original ResearchConceptsReplicase proteinsReplication complexMembrane-bound replication complexesRNA synthesisViral replicase proteinsRNA-dependent RNA polymerase activityViral replication complexFlavivirus RNA synthesisCell nucleus functionsRNA polymerase activityReplicase complexHost cytoplasmNuclear matrixNuclear localizationNuclear locationPeripheral laminaIsolated nucleiImmunoelectron microscopyPolymerase activityJapanese encephalitis virusFlavivirus RNAInfected cellsProteinAbsolute requirementViral RNA
2003
Characterization of RNA synthesis, replication mechanism, and in vitro RNA-dependent RNA polymerase activity of japanese encephalitis virus
Uchil P, Satchidanandam V. Characterization of RNA synthesis, replication mechanism, and in vitro RNA-dependent RNA polymerase activity of japanese encephalitis virus. Virology 2003, 307: 358-371. PMID: 12667804, DOI: 10.1016/s0042-6822(02)00130-7.Peer-Reviewed Original Research