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 functionRetroviruses 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 contactCD169LymphocytesTRIM 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
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
2008
Retroviruses Human Immunodeficiency Virus and Murine Leukemia Virus Are Enriched in Phosphoinositides
Chan R, Uchil PD, Jin J, Shui G, Ott DE, Mothes W, Wenk MR. Retroviruses Human Immunodeficiency Virus and Murine Leukemia Virus Are Enriched in Phosphoinositides. Journal Of Virology 2008, 82: 11228-11238. PMID: 18799574, PMCID: PMC2573248, DOI: 10.1128/jvi.00981-08.Peer-Reviewed Original ResearchConceptsPlasma membraneMurine leukemia virusHIV-1 buddingLipid contentLeukemia virusMass spectrometry analysisCholesterol-rich regionsOverall lipid contentCell peripheryMutant virionsLipid envelopeTotal lipid contentPhosphorylated derivativesSpectrometry analysisPhosphoinositideRetrovirusesMembraneCellsMatrix domainParticle releaseHuman immunodeficiency virus type 1Immunodeficiency virus type 1VirusVirus type 1PhosphatidylinositolMurine 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