Featured Publications
In 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 functionA 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 1CD169TRIM5 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 screenReleaseCellsProtein
2015
TRIM5 Retroviral Restriction Activity Correlates with the Ability To Induce Innate Immune Signaling
Lascano J, Uchil PD, Mothes W, Luban J. TRIM5 Retroviral Restriction Activity Correlates with the Ability To Induce Innate Immune Signaling. Journal Of Virology 2015, 90: 308-316. PMID: 26468522, PMCID: PMC4702541, DOI: 10.1128/jvi.02496-15.Peer-Reviewed Original ResearchConceptsInnate immune signalingImmune signalingHIV-1 transductionHIV-1 restrictionAP-1 signalingViral nucleic acidsAP-1Retroviral capsid latticeAP-1 activationRestriction activityPast infectionProtein cyclophilin ARetrovirus infectionTRIM5Cyclophilin AActivity correlatesInfectionTRIM5 geneReverse transcriptionRetroviral transductionSignalingHost cell nucleusRetroviral capsidActivationTRIM family
2008
Murine Leukemia Virus Spreading in Mice Impaired in the Biogenesis of Secretory Lysosomes and Ca2+-Regulated Exocytosis
Chan WT, Sherer NM, Uchil PD, Novak EK, Swank RT, Mothes W. Murine Leukemia Virus Spreading in Mice Impaired in the Biogenesis of Secretory Lysosomes and Ca2+-Regulated Exocytosis. PLOS ONE 2008, 3: e2713. PMID: 18629000, PMCID: PMC2443282, DOI: 10.1371/journal.pone.0002713.Peer-Reviewed Original ResearchConceptsMurine leukemia virusMultivesicular bodiesPlasma membraneHermansky-Pudlak syndromeLysosome related organellesFunctional AP-3Moloney murine leukemia virusMVB pathwaySynaptotagmin VIILeukemia virusRelated organellesLysosome fusionAP-3Secretory lysosomesMost mutant miceMLV replicationWild-type miceCellular levelBiogenesisModerate reductionEssential roleVirus releaseRelease pathwayMutant miceImmunological alterations