2024
Structure 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 Internalization
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
2021
RSK1 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 166
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 recognitionSubnanometer 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
Sirtuin 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
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
ORF33 and ORF38 of Kaposi's Sarcoma-Associated Herpesvirus Interact and Are Required for Optimal Production of Infectious Progeny Viruses
Wu J, Avey D, Li W, Gillen J, Fu B, Miley W, Whitby D, Zhu F. ORF33 and ORF38 of Kaposi's Sarcoma-Associated Herpesvirus Interact and Are Required for Optimal Production of Infectious Progeny Viruses. Journal Of Virology 2015, 90: 1741-1756. PMID: 26637455, PMCID: PMC4734004, DOI: 10.1128/jvi.02738-15.Peer-Reviewed Original ResearchConceptsProgeny virionsCytoplasmic vesiclesKaposi's Sarcoma-Associated Herpesvirus InteractsDouble null mutantsEarly endosome membraneVirion-containing vesiclesMembranes of vesiclesLytic replicationViral gene expressionProgeny virion productionViral lytic replicationEndosome membraneHerpesvirus assemblyGolgi membranesComponent proteinsIdentical phenotypesGene expressionDelicate regulationVirion proteinsVirus assemblyVirus propagationExact functionInfectious progeny virusMature virionsViral assemblyInhibition of cGAS DNA Sensing by a Herpesvirus Virion Protein
Wu J, Li W, Shao Y, Avey D, Fu B, Gillen J, Hand T, Ma S, Liu X, Miley W, Konrad A, Neipel F, Stürzl M, Whitby D, Li H, Zhu F. Inhibition of cGAS DNA Sensing by a Herpesvirus Virion Protein. Cell Host & Microbe 2015, 18: 333-344. PMID: 26320998, PMCID: PMC4567405, DOI: 10.1016/j.chom.2015.07.015.Peer-Reviewed Original ResearchPhosphoproteomic Analysis of KSHV-Infected Cells Reveals Roles of ORF45-Activated RSK during Lytic Replication
Avey D, Tepper S, Li W, Turpin Z, Zhu F. Phosphoproteomic Analysis of KSHV-Infected Cells Reveals Roles of ORF45-Activated RSK during Lytic Replication. PLOS Pathogens 2015, 11: e1004993. PMID: 26133373, PMCID: PMC4489790, DOI: 10.1371/journal.ppat.1004993.Peer-Reviewed Original ResearchMeSH KeywordsBlotting, WesternCell LineGene Expression Regulation, ViralGene Knockout TechniquesHerpesviridae InfectionsHerpesvirus 8, HumanHost-Parasite InteractionsHumansImmediate-Early ProteinsImmunoprecipitationMass SpectrometryPhosphorylationProteomicsReal-Time Polymerase Chain ReactionReverse Transcriptase Polymerase Chain ReactionRibosomal Protein S6 Kinases, 90-kDaTransfectionVirus ReplicationConceptsKaposi's Sarcoma-Associated HerpesvirusKSHV lytic replicationProgeny virion productionKSHV ORF45Putative substratesRSK activityExtracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) pathwayGene expressionEfficient KSHV lytic replicationLytic replicationP90 ribosomal S6 kinaseMitogen-activated protein kinase pathwayRSK-dependent phosphorylationHost cell machineryRibosomal S6 kinaseProtein kinase pathwayVirion productionActivation of RSKComplex secondary structureKSHV lytic gene expressionTranscriptional regulatorsDifferential phosphorylationLytic gene expressionCellular genesCell machineryA Survey of the Interactome of Kaposi's Sarcoma-Associated Herpesvirus ORF45 Revealed Its Binding to Viral ORF33 and Cellular USP7, Resulting in Stabilization of ORF33 That Is Required for Production of Progeny Viruses
Gillen J, Li W, Liang Q, Avey D, Wu J, Wu F, Myoung J, Zhu F. A Survey of the Interactome of Kaposi's Sarcoma-Associated Herpesvirus ORF45 Revealed Its Binding to Viral ORF33 and Cellular USP7, Resulting in Stabilization of ORF33 That Is Required for Production of Progeny Viruses. Journal Of Virology 2015, 89: 4918-4931. PMID: 25694600, PMCID: PMC4403494, DOI: 10.1128/jvi.02925-14.Peer-Reviewed Original ResearchConceptsUbiquitin-specific protease 7Kaposi's sarcoma-associated herpesvirusSarcoma-associated herpesvirusKSHV lytic replicationORF45 proteinKaposi's Sarcoma-Associated Herpesvirus ORF45Lytic replicationCarboxyl-terminal 19 amino acidsKSHV ORF45Copurified proteinsConsensus motifMultifunctional proteinKinase proteinInteractomeCarboxyl terminusKSHV genomeORF45Tegument proteinsWeight complexesProtein accumulationORF33Progeny virionsAmino acidsHuman cancersProtein
2014
Activation of p90 Ribosomal S6 Kinases by ORF45 of Kaposi's Sarcoma-Associated Herpesvirus Is Critical for Optimal Production of Infectious Viruses
Fu B, Kuang E, Li W, Avey D, Li X, Turpin Z, Valdes A, Brulois K, Myoung J, Zhu F. Activation of p90 Ribosomal S6 Kinases by ORF45 of Kaposi's Sarcoma-Associated Herpesvirus Is Critical for Optimal Production of Infectious Viruses. Journal Of Virology 2014, 89: 195-207. PMID: 25320298, PMCID: PMC4301102, DOI: 10.1128/jvi.01937-14.Peer-Reviewed Original ResearchConceptsRibosomal S6 kinaseP90 ribosomal S6 kinaseKaposi's sarcoma-associated herpesvirusViral gene expressionKSHV lytic replicationSarcoma-associated herpesvirusRSK activationS6 kinaseGene expressionVirus-infected cellsLytic reactivationWild-type virus-infected cellsMutant virus-infected cellsBacterial artificial chromosomeAlanine-scanning mutagenesisLytic replicationCritical rolePhosphoproteomic profilesArtificial chromosomesKinase ERKScanning mutagenesisProgeny viral particlesKSHV genomeInfectious progeny virionsORF45