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 contactCD169Lymphocytes
2023
PLSCR1 is a cell-autonomous defence factor against SARS-CoV-2 infection
Xu D, Jiang W, Wu L, Gaudet R, Park E, Su M, Cheppali S, Cheemarla N, Kumar P, Uchil P, Grover J, Foxman E, Brown C, Stansfeld P, Bewersdorf J, Mothes W, Karatekin E, Wilen C, MacMicking J. PLSCR1 is a cell-autonomous defence factor against SARS-CoV-2 infection. Nature 2023, 619: 819-827. PMID: 37438530, PMCID: PMC10371867, DOI: 10.1038/s41586-023-06322-y.Peer-Reviewed Original ResearchConceptsC-terminal β-barrel domainSpike-mediated fusionCell-autonomous defenseLarge-scale exome sequencingΒ-barrel domainGenome-wide CRISPRSARS-CoV-2 infectionHost cell cytosolScramblase activityPhospholipid scramblaseLive SARS-CoV-2 infectionHuman lung epitheliumPLSCR1SARS-CoV-2 USASingle-molecule switchingSARS-CoV-2 variantsExome sequencingHuman populationRestriction factorsViral RNANew SARS-CoV-2 variantsSARS-CoV-2Robust activityLung epitheliumDefense factors
2020
Real-Time Conformational Dynamics of SARS-CoV-2 Spikes on Virus Particles
Lu M, Uchil PD, Li W, Zheng D, Terry DS, Gorman J, Shi W, Zhang B, Zhou T, Ding S, Gasser R, Prévost J, Beaudoin-Bussières G, Anand SP, Laumaea A, Grover JR, Liu L, Ho DD, Mascola JR, Finzi A, Kwong PD, Blanchard SC, Mothes W. Real-Time Conformational Dynamics of SARS-CoV-2 Spikes on Virus Particles. Cell Host & Microbe 2020, 28: 880-891.e8. PMID: 33242391, PMCID: PMC7664471, DOI: 10.1016/j.chom.2020.11.001.Peer-Reviewed Original ResearchConceptsSingle-molecule fluorescence resonance energy transferReceptor-binding domainSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Conformational dynamicsSyndrome coronavirus 2SARS-CoV-2 spikeCoronavirus disease 2019Distinct conformational statesMechanism of neutralizationHuman receptor angiotensinVirus particlesConvalescent plasmaCoronavirus 2Disease 2019Enzyme 2Fluorescence resonance energy transferReceptor angiotensinVaccine developmentImmunogen designViral entryConformational changesDistinct conformationsS recognition
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
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