2024
Inducible cell lines producing replication-defective human immunodeficiency virus particles containing envelope glycoproteins stabilized in a pretriggered conformation.
Ding H, Nguyen H, Li W, Deshpande A, Zhang S, Jiang F, Zhang Z, Anang S, Mothes W, Sodroski J, Kappes J. Inducible cell lines producing replication-defective human immunodeficiency virus particles containing envelope glycoproteins stabilized in a pretriggered conformation. Journal Of Virology 2024, e0172024. PMID: 39508605, DOI: 10.1128/jvi.01720-24.Peer-Reviewed Original ResearchHuman immunodeficiency virusEnv trimersNeutralizing antibodiesHIV-1Virus-like particlesEnvelope glycoproteinEnv conformationImmunodeficiency virusInducible cell linesCell linesImmune systemEffective HIV/AIDS vaccineHIV-1 persistenceHuman immunodeficiency virus particlesEnvelope glycoprotein spikeHIV-1 EnvPoorly neutralizing antibodiesHIV-like particlesHIV-1 particlesDefective virus-like particlesHost immune systemEnv immunogensHIV/AIDS vaccineCreation of stable cell linesHost cell receptorsBeta Spike-Presenting SARS-CoV-2 Virus-like Particle Vaccine Confers Broad Protection against Other VOCs in Mice
Ullah I, Symmes K, Keita K, Zhu L, Grunst M, Li W, Mothes W, Kumar P, Uchil P. Beta Spike-Presenting SARS-CoV-2 Virus-like Particle Vaccine Confers Broad Protection against Other VOCs in Mice. Vaccines 2024, 12: 1007. PMID: 39340037, PMCID: PMC11435481, DOI: 10.3390/vaccines12091007.Peer-Reviewed Original ResearchImmune responseVirus-like particlesBeta spikesCross-protective immune responsesSARS-CoV-2 immunitySARS-CoV-2Effective immune responseEffective humoral immune responseHumoral immune responseAncestral spikeT cellsVaccination regimenSARS-CoV-2 virus-like particlesVaccine platformMouse modelVariant spike proteinsOmicron spikeBeta variantDisease burdenNon-infectiousReduce virus spreadImmunityVariant spikesFusion glycoproteinSpike proteinStructure and inhibition of SARS-CoV-2 spike refolding in membranes
Grunst M, Qin Z, Dodero-Rojas E, Ding S, Prévost J, Chen Y, Hu Y, Pazgier M, Wu S, Xie X, Finzi A, Onuchic J, Whitford P, Mothes W, Li W. Structure and inhibition of SARS-CoV-2 spike refolding in membranes. Science 2024, 385: 757-765. PMID: 39146425, PMCID: PMC11449073, DOI: 10.1126/science.adn5658.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin-Converting Enzyme 2Antibodies, NeutralizingAntibodies, ViralBetacoronavirusCell MembraneCOVID-19Cryoelectron MicroscopyElectron Microscope TomographyHumansMolecular Dynamics SimulationPeptidyl-Dipeptidase AProtein DomainsProtein MultimerizationProtein RefoldingSARS-CoV-2Spike Glycoprotein, CoronavirusVirus InternalizationViral spike-receptor interactions monitored by cryo-electron tomograpy on membranes
Mothes W, Li W, Grunst M, Qin Z, Nand E. Viral spike-receptor interactions monitored by cryo-electron tomograpy on membranes. Biophysical Journal 2024, 123: 24a. DOI: 10.1016/j.bpj.2023.11.251.Peer-Reviewed Original ResearchBioorthogonal click labeling of an amber-free HIV-1 provirus for in-virus single molecule imaging
Ao Y, Grover J, Gifford L, Han Y, Zhong G, Katte R, Li W, Bhattacharjee R, Zhang B, Sauve S, Qin W, Ghimire D, Haque M, Arthos J, Moradi M, Mothes W, Lemke E, Kwong P, Melikyan G, Lu M. Bioorthogonal click labeling of an amber-free HIV-1 provirus for in-virus single molecule imaging. Cell Chemical Biology 2024, 31: 487-501.e7. PMID: 38232732, PMCID: PMC10960674, DOI: 10.1016/j.chembiol.2023.12.017.Peer-Reviewed Original ResearchHIV-1Human immunodeficiency virus-1HIV-1 provirusMinimally invasive approachImmunodeficiency virus-1HIV-1 systemInvasive approachImmune evasionEnvVirus 1Virus entryStudies of virus entryCell entrySingle-molecule Forster resonance energy transferStructural dynamicsSingle molecule imagingMultiple conformational statesForster resonance energy transferCellsClick chemistryVirion internalizationResonance energy transferMolecule imagingEnergy transferLabeling of proteins
2023
HIV-1 Env trimers asymmetrically engage CD4 receptors in membranes
Li W, Qin Z, Nand E, Grunst M, Grover J, Bess J, Lifson J, Zwick M, Tagare H, Uchil P, Mothes W. HIV-1 Env trimers asymmetrically engage CD4 receptors in membranes. Nature 2023, 623: 1026-1033. PMID: 37993716, PMCID: PMC10686830, DOI: 10.1038/s41586-023-06762-6.Peer-Reviewed Original ResearchConceptsHIV-1 Env trimersCD4 moleculeHuman immunodeficiency virus-1 (HIV-1) infectionEnv trimersAntibody-mediated immune responsesEnv-CD4 interactionVirus-1 infectionVaccine immunogen designViral envelope glycoproteinsHIV-1Immune responseCD4 receptorImmunogen designEnvelope glycoproteinVirus-like particlesCD4EnvHost cell membrane
2022
The flagellar motor protein FliL forms a scaffold of circumferentially positioned rings required for stator activation
Tachiyama S, Chan KL, Liu X, Hathroubi S, Li W, Peterson B, Khan M, Ottemann K, Liu J, Roujeinikova A. The flagellar motor protein FliL forms a scaffold of circumferentially positioned rings required for stator activation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2118401119. PMID: 35046042, PMCID: PMC8794807, DOI: 10.1073/pnas.2118401119.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceBacterial Physiological PhenomenaBacterial ProteinsFlagellaHelicobacter pyloriMembrane ProteinsModels, MolecularMolecular Motor ProteinsMultiprotein ComplexesProtein BindingProtein ConformationProtein Interaction Domains and MotifsProtein TransportStructure-Activity RelationshipConceptsStator unitsStomatin/prohibitin/flotillin/HflK/C (SPFH) domainWild-type cellsSignificant structural similarityPeriplasmic domainAssembly factorsFlagellar motorAccessory proteinsFliLLinker regionActive conformationFlagellar baseC-domainMotBStructural similarityStator assemblyProteinPutative mechanismsElectron tomography reconstructionsIntact motorCellsActivationDomainMotAHelix
2021
Structural basis and mode of action for two broadly neutralizing antibodies against SARS-CoV-2 emerging variants of concern
Li W, Chen Y, Prévost J, Ullah I, Lu M, Gong SY, Tauzin A, Gasser R, Vézina D, Anand SP, Goyette G, Chaterjee D, Ding S, Tolbert WD, Grunst MW, Bo Y, Zhang S, Richard J, Zhou F, Huang RK, Esser L, Zeher A, Côté M, Kumar P, Sodroski J, Xia D, Uchil PD, Pazgier M, Finzi A, Mothes W. Structural basis and mode of action for two broadly neutralizing antibodies against SARS-CoV-2 emerging variants of concern. Cell Reports 2021, 38: 110210. PMID: 34971573, PMCID: PMC8673750, DOI: 10.1016/j.celrep.2021.110210.Peer-Reviewed Original ResearchVariants of concernProtective immune responseReceptor-binding domainImmune responseImmunogen designSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Syndrome coronavirus 2Mode of actionSARS-CoV-2 spikeSARS-CoV-2Vaccine immunogen designAntibody therapyCoronavirus 2Β-coronavirusMonoclonal antibodiesS1 subunitS2 subunitAntibodiesTherapyVariantsRSK1 SUMOylation is required for KSHV lytic replication
Liu Z, Liu C, Wang X, Li W, Zhou J, Dong P, Xiao M, Wang C, Zhang Y, Fu J, Zhu F, Liang Q. RSK1 SUMOylation is required for KSHV lytic replication. PLOS Pathogens 2021, 17: e1010123. PMID: 34871326, PMCID: PMC8675914, DOI: 10.1371/journal.ppat.1010123.Peer-Reviewed Original ResearchConceptsSUMO-interacting motifKSHV lytic replicationKaposi's sarcoma-associated herpesvirusSarcoma-associated herpesvirusEfficient KSHV lytic replicationLytic replicationDownstream substrate phosphorylationAmino acid position 166SUMO-SIM interactionsOverall phosphorylation levelMultiple cellular processesPost-translational modificationsKSHV ORF45Substrate phosphorylationSUMO modificationCellular processesDownstream substratesRSK1 activationDownstream kinasesMAPK pathwaySequence analysisRSK1SUMOylationPhosphorylation levelsPosition 166Real-Time Conformational Dynamics of SARS-CoV-2 Spikes on Virus Particles
Lu M, Uchil P, Li W, Terry D, Gorman J, Zhang B, Zhou T, Ding S, Liu L, Ho D, Mascola J, Finzi A, Kwong P, Blanchard S, Mothes W. Real-Time Conformational Dynamics of SARS-CoV-2 Spikes on Virus Particles. Biophysical Journal 2021, 120: 276a. PMCID: PMC7879775, DOI: 10.1016/j.bpj.2020.11.1757.Peer-Reviewed Original Research
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 recognitionThree STIGMA AND STYLE STYLISTs Pattern the Fine Architectures of Apical Gynoecium and Are Critical for Male Gametophyte-Pistil Interaction
Li W, Huang X, Zou J, Wu J, Jiao H, Peng X, Sun M. Three STIGMA AND STYLE STYLISTs Pattern the Fine Architectures of Apical Gynoecium and Are Critical for Male Gametophyte-Pistil Interaction. Current Biology 2020, 30: 4780-4788.e5. PMID: 33007250, DOI: 10.1016/j.cub.2020.09.006.Peer-Reviewed Original ResearchConceptsApical gynoeciumSexual reproductionPollen tubesPlant sexual reproductionTransmitting tract tissueEfficient sexual reproductionSame regulatory pathwayFusion of carpelsNovel molecular mechanismPollen tube growthGene familyPlant fertilityDouble mutantTranscription factorsTransmitting tractRegulatory pathwaysMolecular mechanismsTube growthGynoeciumCell typesFine architectureCell expansionCritical roleReproductionTissue distributionSubnanometer structures of HIV-1 envelope trimers on aldrithiol-2-inactivated virus particles
Li Z, Li W, Lu M, Bess J, Chao CW, Gorman J, Terry DS, Zhang B, Zhou T, Blanchard SC, Kwong PD, Lifson JD, Mothes W, Liu J. Subnanometer structures of HIV-1 envelope trimers on aldrithiol-2-inactivated virus particles. Nature Structural & Molecular Biology 2020, 27: 726-734. PMID: 32601441, PMCID: PMC8138683, DOI: 10.1038/s41594-020-0452-2.Peer-Reviewed Original Research
2019
High-resolution view of the type III secretion export apparatus in situ reveals membrane remodeling and a secretion pathway
Butan C, Lara-Tejero M, Li W, Liu J, Galán JE. High-resolution view of the type III secretion export apparatus in situ reveals membrane remodeling and a secretion pathway. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 24786-24795. PMID: 31744874, PMCID: PMC6900529, DOI: 10.1073/pnas.1916331116.Peer-Reviewed Original ResearchSirtuin 6 Attenuates Kaposi's Sarcoma-Associated Herpesvirus Reactivation by Suppressing Ori-Lyt Activity and Expression of RTA
Hu M, Armstrong N, Seto E, Li W, Zhu F, Wang P, Tang Q. Sirtuin 6 Attenuates Kaposi's Sarcoma-Associated Herpesvirus Reactivation by Suppressing Ori-Lyt Activity and Expression of RTA. Journal Of Virology 2019, 93: 10.1128/jvi.02200-18. PMID: 30651359, PMCID: PMC6430549, DOI: 10.1128/jvi.02200-18.Peer-Reviewed Original ResearchMeSH KeywordsCell LineCell Line, TumorDNA ReplicationDNA, ViralGene Expression Regulation, ViralHEK293 CellsHerpesvirus 8, HumanHumansImmediate-Early ProteinsNuclear ProteinsPromoter Regions, GeneticRepressor ProteinsRNA, Small InterferingSarcoma, KaposiSirtuinsTrans-ActivatorsViral ProteinsVirus LatencyVirus ReplicationConceptsKaposi's sarcoma-associated herpesvirusViral DNA replicationReactivation of KSHVSarcoma-associated herpesvirusDNA replicationGene expressionViral gene expressionKSHV promotersHistone deacetylasesPromoter activityKSHV reactivationKaposi's Sarcoma-Associated Herpesvirus ReactivationCell linesDepletion of SIRT6KSHV gene expressionChromatin immunoprecipitation assaysExpression of RTAViral protein productionReduced gene expressionCellular regulatorsImmunoprecipitation assaysOverexpression of SIRT6Multiple promotersKSHV genomeOri-Lyt
2018
Visualization of the type III secretion mediated Salmonella–host cell interface using cryo-electron tomography
Park D, Lara-Tejero M, Waxham MN, Li W, Hu B, Galán JE, Liu J. Visualization of the type III secretion mediated Salmonella–host cell interface using cryo-electron tomography. ELife 2018, 7: e39514. PMID: 30281019, PMCID: PMC6175578, DOI: 10.7554/elife.39514.Peer-Reviewed Original ResearchConceptsCryo-electron tomographyEffector translocationBacterial-host cell contactType III protein secretion systemProtein secretion systemHost cell interfaceProtein secretion machinesCell membraneComplex host-pathogen interactionsType III secretionHost-pathogen interactionsHost cell membraneTarget cell membraneNegative bacterial pathogensTranslocon poreSecretion machineEffector proteinsSecretion systemHost cellsBacterial pathogensCell contactCell interfaceIntimate associationTranslocationBacteria
2017
Correction for Avey et al., “Discovery of a Coregulatory Interaction between Kaposi's Sarcoma-Associated Herpesvirus ORF45 and the Viral Protein Kinase ORF36”
Avey D, Tepper S, Pifer B, Bahga A, Williams H, Gillen J, Li W, Ogden S, Zhu F. Correction for Avey et al., “Discovery of a Coregulatory Interaction between Kaposi's Sarcoma-Associated Herpesvirus ORF45 and the Viral Protein Kinase ORF36”. Journal Of Virology 2017, 91: 10.1128/jvi.01484-17. PMID: 29138329, PMCID: PMC5686716, DOI: 10.1128/jvi.01484-17.Peer-Reviewed Original Research
2016
Discovery of a Coregulatory Interaction between Kaposi's Sarcoma-Associated Herpesvirus ORF45 and the Viral Protein Kinase ORF36
Avey D, Tepper S, Pifer B, Bahga A, Williams H, Gillen J, Li W, Ogden S, Zhu F. Discovery of a Coregulatory Interaction between Kaposi's Sarcoma-Associated Herpesvirus ORF45 and the Viral Protein Kinase ORF36. Journal Of Virology 2016, 90: 5953-5964. PMID: 27099309, PMCID: PMC4907238, DOI: 10.1128/jvi.00516-16.Peer-Reviewed Original ResearchConceptsKaposi's sarcoma-associated herpesvirusKSHV ORF36Viral protein kinaseSarcoma-associated herpesvirusProtein kinaseKSHV lytic replicationKaposi's Sarcoma-Associated Herpesvirus ORF45Infectious progeny virionsHerpesvirus protein kinasesProgeny virionsLytic replicationKinase-dead mutantBacterial artificial chromosome mutagenesisBasic N-terminusCoregulatory interactionsChromosome mutagenesisORF45 proteinViral life cycleAcidic patchKSHV proteinsORF36Human tumor virusKinase activityORF45N-terminusKaposi's Sarcoma-Associated Herpesvirus Inhibitor of cGAS (KicGAS), Encoded by ORF52, Is an Abundant Tegument Protein and Is Required for Production of Infectious Progeny Viruses
Li W, Avey D, Fu B, Wu J, Ma S, Liu X, Zhu F. Kaposi's Sarcoma-Associated Herpesvirus Inhibitor of cGAS (KicGAS), Encoded by ORF52, Is an Abundant Tegument Protein and Is Required for Production of Infectious Progeny Viruses. Journal Of Virology 2016, 90: 5329-5342. PMID: 27009954, PMCID: PMC4934757, DOI: 10.1128/jvi.02675-15.Peer-Reviewed Original ResearchConceptsKaposi's sarcoma-associated herpesvirusSarcoma-associated herpesvirusImmune evasion functionsViral particlesKSHV replicationTegument proteinsInfectious progeny virusInfectious viral particlesPrimary infectionSpecific monoclonal antibodiesExtracellular virionsViral life cycleImmune evasionKSHV life cycleTherapeutic interventionsViral replicationNovel targetKSHV lytic replicationMonoclonal antibodiesCytosolic DNAReduced virion productionLytic replicationProgeny virusVirion proteinsVirion production
2015
Mono-ubiquitylated ORF45 Mediates Association of KSHV Particles with Internal Lipid Rafts for Viral Assembly and Egress
Wang X, Zhu N, Li W, Zhu F, Wang Y, Yuan Y. Mono-ubiquitylated ORF45 Mediates Association of KSHV Particles with Internal Lipid Rafts for Viral Assembly and Egress. PLOS Pathogens 2015, 11: e1005332. PMID: 26650119, PMCID: PMC4674120, DOI: 10.1371/journal.ppat.1005332.Peer-Reviewed Original ResearchKaposi's sarcoma-associated herpesvirusLipid raftsSarcoma-associated herpesvirusFinal envelopmentVesicle membraneRecombinant Kaposi's sarcoma-associated herpesvirusTrans-Golgi networkCytoplasmic membrane vesiclesCellular cargo transportVirion particlesInfectious virion particlesHost cell membraneViral particlesTrans-GolgiEndosome vesiclesLR associationBudding processORF45Virion assemblyWild typeIntracellular signalingTegument proteinsCellular membranesMembrane vesiclesViral assembly