2024
UBXN9 governs GLUT4-mediated spatial confinement of RIG-I-like receptors and signaling
Harrison A, Yang D, Cahoon J, Geng T, Cao Z, Karginov T, Hu Y, Li X, Chiari C, Qyang Y, Vella A, Fan Z, Vanaja S, Rathinam V, Witczak C, Bogan J, Wang P. UBXN9 governs GLUT4-mediated spatial confinement of RIG-I-like receptors and signaling. Nature Immunology 2024, 25: 2234-2246. PMID: 39567760, DOI: 10.1038/s41590-024-02004-7.Peer-Reviewed Original ResearchA substitution at the cytoplasmic tail of the spike protein enhances SARS-CoV-2 infectivity and immunogenicity
Li Y, Zhang X, Tai W, Zhuang X, Shi H, Liao S, Yu X, Mei R, Chen X, Huang Y, Liu Y, Liu J, Liu Y, Zhu Y, Wang P, Tian M, Yu G, Li L, Cheng G. A substitution at the cytoplasmic tail of the spike protein enhances SARS-CoV-2 infectivity and immunogenicity. EBioMedicine 2024, 110: 105437. PMID: 39531918, DOI: 10.1016/j.ebiom.2024.105437.Peer-Reviewed Original ResearchS proteinCytoplasmic tailFERM-binding motifTrans-complementation systemSpike proteinAmino acid substitutionsProline-to-leucine substitutionSystematic bioinformatics analysisHigh-frequency mutationsSARS-CoV-2 virionsBinding motifAcid substitutionsSARS-CoV-2Natural selectionBioinformatics analysisEzrin/radixin/moesin proteinsMolecular mechanismsMutationsOmicron variantProteinVaccine developmentMRNA vaccinesGlobal disseminationSARS-CoV-2 Omicron sublineagesSublineagesAutoregulated splicing of TRA2β programs T cell fate in response to antigen-receptor stimulation
Karginov T, Ménoret A, Leclair N, Harrison A, Chandiran K, Suarez-Ramirez J, Yurieva M, Karlinsey K, Wang P, O'Neill R, Murphy P, Adler A, Cauley L, Anczuków O, Zhou B, Vella A. Autoregulated splicing of TRA2β programs T cell fate in response to antigen-receptor stimulation. Science 2024, 385: eadj1979. PMID: 39265028, DOI: 10.1126/science.adj1979.Peer-Reviewed Original ResearchConceptsRNA-binding proteinsT cell fateT cell receptor sensitivityT cell receptorPoison exonGenomes of jawed vertebratesPosttranscriptional regulatory mechanismsResponse to antigen receptor stimulationAntigen receptor stimulationTranscriptional regulationJawed vertebratesAlternative splicingSignaling transcriptsT cell survivalRegulatory mechanismsTCR sensitivitySplicingT-cell receptor gene rearrangementEffector T cell expansionT cell responses to antigenTRA2BT cell expansionResponse to antigenGene rearrangementsHistocompatibility complexUBXN3B is crucial for B lymphopoiesis
Geng T, Yang D, Lin T, Harrison A, Wang B, Cao Z, Torrance B, Fan Z, Wang K, Wang Y, Yang L, Haynes L, Cheng G, Vella A, Flavell R, Pereira J, Fikrig E, Wang P. UBXN3B is crucial for B lymphopoiesis. EBioMedicine 2024, 106: 105248. PMID: 39018756, PMCID: PMC11287013, DOI: 10.1016/j.ebiom.2024.105248.Peer-Reviewed Original ResearchUbiquitin regulatory XPre-BCR signalingB cell receptorB lymphopoiesisKnockout miceValosin-containing proteinCaspase-3 protein levelsCell cycle arrestBone marrow transferNormal B lymphopoiesisUbiquitin ligaseIncreased viral loadCell-intrinsic mannerPathogenesis of severe acute respiratory syndrome coronavirus 2RNA sequencingCycle arrestDNA virusesCell survivalMarrow transferMultiple virusesSingle-cellImmunofluorescence microscopyViral loadMature BRespiratory virusesA naturally isolated symbiotic bacterium suppresses flavivirus transmission by Aedes mosquitoes
Zhang L, Wang D, Shi P, Li J, Niu J, Chen J, Wang G, Wu L, Chen L, Yang Z, Li S, Meng J, Ruan F, He Y, Zhao H, Ren Z, Wang Y, Liu Y, Shi X, Wang Y, Liu Q, Li J, Wang P, Wang J, Zhu Y, Cheng G. A naturally isolated symbiotic bacterium suppresses flavivirus transmission by Aedes mosquitoes. Science 2024, 384: eadn9524. PMID: 38669573, DOI: 10.1126/science.adn9524.Peer-Reviewed Original ResearchConceptsColony forming unitsFlavivirus envelope proteinCommensal microbiotaIrreversible conformational changesGlucose dehydrogenaseMosquito gutConformational changesGut lumenPrevent viral infectionGutBacteriumFlavivirus transmissionEnvelope proteinsVector competencePrevent viral entryViral entryRefractory to infectionDengue virusForming unitsField mosquitoesTransmission of dengue virusFlavivirusesMosquitoesSemifield conditionsAdult mosquitoesAn evolutionarily conserved ubiquitin ligase drives infection and transmission of flaviviruses
Wu L, Zhang L, Feng S, Chen L, Lin C, Wang G, Zhu Y, Wang P, Cheng G. An evolutionarily conserved ubiquitin ligase drives infection and transmission of flaviviruses. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2317978121. PMID: 38593069, PMCID: PMC11032495, DOI: 10.1073/pnas.2317978121.Peer-Reviewed Original ResearchConceptsNonstructural proteinsSingle-stranded RNA genomeER-associated degradationE3 ligase HRD1Individual functional proteinsFlavivirus infectionCellular fitnessRNA genomeUbiquitin systemFlavivirus NS4AFunctional proteinsFlavivirus proteinsLysine residuesMammalian hostsMosquito-borne flavivirusSmall molecule inhibitorsStructural proteinsHrd1Viral proteinsProgeny virionsUbiquitinPotential therapeutic targetDENV2 infectionProteinNS4AA mosquito salivary protein-driven influx of myeloid cells facilitates flavivirus transmission
Wang Z, Nie K, Liang Y, Niu J, Yu X, Zhang O, Liu L, Shi X, Wang Y, Feng X, Zhu Y, Wang P, Cheng G. A mosquito salivary protein-driven influx of myeloid cells facilitates flavivirus transmission. The EMBO Journal 2024, 43: 1690-1721. PMID: 38378891, PMCID: PMC11066113, DOI: 10.1038/s44318-024-00056-x.Peer-Reviewed Original ResearchMyeloid cellsExpression of neutrophil chemoattractantsViral transmissionInflux of myeloid cellsMosquito bite siteSalivary componentsInflux of neutrophilsSkin-resident macrophagesPotential prophylactic targetsFlavivirus transmissionNF-kB signalingMechanism of actionProphylactic targetsSystemic disseminationRecruits proteinsSalivary factorsLocal infectionNeutrophil chemoattractantMammalian hostsEfficient viral transmissionPhytochemical resveratrolDengue virusBite siteTransmission of ZikaProteinUBR5 promotes antiviral immunity by disengaging the transcriptional brake on RIG-I like receptors
Yang D, Geng T, Harrison A, Cahoon J, Xing J, Jiao B, Wang M, Cheng C, Hill R, Wang H, Vella A, Cheng G, Wang Y, Wang P. UBR5 promotes antiviral immunity by disengaging the transcriptional brake on RIG-I like receptors. Nature Communications 2024, 15: 780. PMID: 38278841, PMCID: PMC10817939, DOI: 10.1038/s41467-024-45141-1.Peer-Reviewed Original ResearchConceptsUbiquitin protein ligase E3 component N-recognin 5RIG-IImmune response to RNA virusesResponse to RNA virusesRetinoic acid-inducible gene ILysine 63-linked ubiquitinationAntiviral immune responseRNA virus infectionViral RNA sensorsKnockout cell linesInitiation of antiviral immune responsesBoost antiviral immune responseImmune responsePosttranslational regulationTranscriptional brakeGene IEpigenetic repressorsRNA virusesDe-SUMOylationRNA sensorsUbiquitinWild type littermatesIncreased viral replicationTRIM28Transcription
2022
UBXN3B Controls Immunopathogenesis of Arthritogenic Alphaviruses by Maintaining Hematopoietic Homeostasis
Geng T, Yang D, Lin T, Cahoon J, Wang P. UBXN3B Controls Immunopathogenesis of Arthritogenic Alphaviruses by Maintaining Hematopoietic Homeostasis. MBio 2022, 13: e02687-22. PMID: 36377866, PMCID: PMC9765034, DOI: 10.1128/mbio.02687-22.Peer-Reviewed Original ResearchConceptsUbiquitin regulatory X domain-containing proteinDomain-containing proteinsDiverse cellular processesCell-intrinsic mannerCellular processesHematopoietic homeostasisPhysiological functionsRNA virus replicationEssential roleControl of infectionChikungunya virusHuman genomeArthritogenic alphavirusesImmune responseCHIKV replicationDNA virusesRNA virusesInnate immune responseVirus-specific immunoglobulin GO'nyong'nyong virusLong-term neurological disordersSignificant public health problemSerum cytokine levelsSpecific antiviral drugsHigh viral loadQuantitative Analysis of B-Cell Subpopulations in Bone Marrow by Flow Cytometry
Geng T, Wang P. Quantitative Analysis of B-Cell Subpopulations in Bone Marrow by Flow Cytometry. Methods In Molecular Biology 2022, 2585: 71-77. PMID: 36331766, DOI: 10.1007/978-1-0716-2760-0_8.Peer-Reviewed Original ResearchMosquito-borne pathogens hijack human body odors to promote transmission
Wang P, Cheng G. Mosquito-borne pathogens hijack human body odors to promote transmission. Science China Life Sciences 2022, 66: 180-182. PMID: 36346549, DOI: 10.1007/s11427-022-2231-7.Peer-Reviewed Original ResearchNeighboring mutation‐mediated enhancement of dengue virus infectivity and spread
Chen L, Zhang X, Guo X, Peng W, Zhu Y, Wang Z, Yu X, Shi H, Li Y, Zhang L, Wang L, Wang P, Cheng G. Neighboring mutation‐mediated enhancement of dengue virus infectivity and spread. EMBO Reports 2022, 23: embr202255671. PMID: 36197120, PMCID: PMC9638853, DOI: 10.15252/embr.202255671.Peer-Reviewed Original ResearchThe noncanonical inflammasome in health and disease
Cahoon J, Yang D, Wang P. The noncanonical inflammasome in health and disease. Infectious Medicine 2022, 1: 208-216. PMID: 38077630, PMCID: PMC10699704, DOI: 10.1016/j.imj.2022.09.001.Peer-Reviewed Original ResearchNoncanonical inflammasomeRapid cellular responsesKey cellular regulatorsInnate immune signalingMechanism of activationAdaptor proteinCellular regulatorsPattern recognition receptorsNon-canonical inflammasomeImmune signalingCaspase-4Cellular responsesRecognition receptorsSubsequent maturationNegative bacterial infectionsCaspase-1Inflammatory cytokinesInflammatory diseasesInflammasomeBacterial infectionsRecent advancesDiseaseSignalingRegulatorProteinA Retinol Derivative Inhibits SARS-CoV-2 Infection by Interrupting Spike-Mediated Cellular Entry
Tong L, Wang L, Liao S, Xiao X, Qu J, Wu C, Zhu Y, Tai W, Huang Y, Wang P, Li L, Zhang R, Xiang Y, Cheng G. A Retinol Derivative Inhibits SARS-CoV-2 Infection by Interrupting Spike-Mediated Cellular Entry. MBio 2022, 13: e01485-22. PMID: 35862773, PMCID: PMC9426596, DOI: 10.1128/mbio.01485-22.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 variantsSARS-CoV-2 infectionPotent antiviral activitySevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Inhibits SARS-CoV-2 infectionAntiviral activityRespiratory syndrome coronavirus 2Retinoic acidLower respiratory tractSyndrome coronavirus 2Coronavirus disease 2019Multiple organ systemsVitamin A derivativesCOVID-19 diseaseSpike protein trimerS trimerCoronavirus 2Respiratory tractDisease 2019Vitamin AActive metaboliteOrgan systemsEtiological agentTherapeutic antibodiesA volatile from the skin microbiota of flavivirus-infected hosts promotes mosquito attractiveness
Zhang H, Zhu Y, Liu Z, Peng Y, Peng W, Tong L, Wang J, Liu Q, Wang P, Cheng G. A volatile from the skin microbiota of flavivirus-infected hosts promotes mosquito attractiveness. Cell 2022, 185: 2510-2522.e16. PMID: 35777355, DOI: 10.1016/j.cell.2022.05.016.Peer-Reviewed Original ResearchSkin microbiotaMosquito-transmitted flavivirusDengue patientsFlavivirus infectionFlavivirus life cycleDietary administrationHealthy peopleCommensal bacteriaZika virusHost skinMosquito attractivenessArboviral transmissionRELMαAedes mosquitoesMicrobiotaMosquito olfactionInfected hostAntimicrobial proteinsHematophagous arthropodsHost-seeking activityMosquitoesIsotretinoinPatientsInfectionMiceLipases secreted by a gut bacterium inhibit arbovirus transmission in mosquitoes
Yu X, Tong L, Zhang L, Yang Y, Xiao X, Zhu Y, Wang P, Cheng G. Lipases secreted by a gut bacterium inhibit arbovirus transmission in mosquitoes. PLOS Pathogens 2022, 18: e1010552. PMID: 35679229, PMCID: PMC9182268, DOI: 10.1371/journal.ppat.1010552.Peer-Reviewed Original ResearchConceptsJapanese encephalitis virusYellow fever virusZika virusDengue virusSindbis virusGlobal public healthBroad-spectrum virucidal activityEffective prophylacticLipase activityViral envelope structureViral infectionSevere human diseasesEncephalitis virusAedes aegypti midgutVirucidal activityEtiological agentTremendous burdenFever virusVirusMost arbovirusesPublic healthVector-borne diseasesAegypti midgutDiseaseVirucidal abilityA glucose-like metabolite deficient in diabetes inhibits cellular entry of SARS-CoV-2
Tong L, Xiao X, Li M, Fang S, Ma E, Yu X, Zhu Y, Wu C, Tian D, Yang F, Sun J, Qu J, Zheng N, Liao S, Tai W, Feng S, Zhang L, Li Y, Wang L, Han X, Sun S, Yang L, Zhong H, Zhao J, Liu W, Liu X, Wang P, Li L, Zhao G, Zhang R, Cheng G. A glucose-like metabolite deficient in diabetes inhibits cellular entry of SARS-CoV-2. Nature Metabolism 2022, 4: 547-558. PMID: 35534727, DOI: 10.1038/s42255-022-00567-z.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Diabetes mellitusDiabetic micePre-existing medical comorbiditiesSARS-CoV-2 infectionSARS-CoV-2 replicationRespiratory tissue damageSevere COVID-19COVID-19 pathogenesisHigh viral loadWild-type miceSARS-CoV-2 loadSARS-CoV-2 spike proteinCOVID-19Effective antiviral activityMedical comorbiditiesDiabetic populationDiabetic patientsNondiabetic miceViral loadAG supplementationSustained supplementationAg levelsHealthy individualsViral infectionIntrinsic cardiac adrenergic cells contribute to LPS-induced myocardial dysfunction
Yang D, Dai X, Xing Y, Tang X, Yang G, Harrison A, Cahoon J, Li H, Lv X, Yu X, Wang P, Wang H. Intrinsic cardiac adrenergic cells contribute to LPS-induced myocardial dysfunction. Communications Biology 2022, 5: 96. PMID: 35079095, PMCID: PMC8789803, DOI: 10.1038/s42003-022-03007-6.Peer-Reviewed Original ResearchConceptsIntrinsic cardiac adrenergic cellsToll-like receptor 4ICA cellsTNF-α productionMyocardial dysfunctionSeptic cardiomyopathyAdrenergic cellsMyocardial TNF-α productionSecretion of NEPotential therapeutic targetΒ1-adrenergic receptorNE biosynthesisTLR4-MyD88Receptor 4Norepinephrine secretionP65 translocationTyrosine hydroxylaseNF-κBTherapeutic targetMitogen-activated protein kinase pathwayDependent protein kinase IILipopolysaccharideDysfunctionProtein kinase IIPathological processes
2021
A human-blood-derived microRNA facilitates flavivirus infection in fed mosquitoes
Zhu Y, Zhang C, Zhang L, Yang Y, Yu X, Wang J, Liu Q, Wang P, Cheng G. A human-blood-derived microRNA facilitates flavivirus infection in fed mosquitoes. Cell Reports 2021, 37: 110091. PMID: 34910910, DOI: 10.1016/j.celrep.2021.110091.Peer-Reviewed Original ResearchSTAT6 Deficiency Attenuates Myeloid Fibroblast Activation and Macrophage Polarization in Experimental Folic Acid Nephropathy
Jiao B, An C, Du H, Tran M, Wang P, Zhou D, Wang Y. STAT6 Deficiency Attenuates Myeloid Fibroblast Activation and Macrophage Polarization in Experimental Folic Acid Nephropathy. Cells 2021, 10: 3057. PMID: 34831280, PMCID: PMC8623460, DOI: 10.3390/cells10113057.Peer-Reviewed Original ResearchConceptsFolic acid nephropathySTAT6 knockout miceM2 macrophage polarizationRenal fibrosis developmentMacrophage polarizationKidney diseaseFibroblast activationKnockout miceRenal fibrosisFibrosis developmentMyeloid fibroblastsEnd-stage kidney diseaseChronic kidney diseaseSevere interstitial fibrosisFibrotic kidney diseaseWild-type miceNovel therapeutic strategiesExtracellular matrix protein productionMatrix protein productionKidney functionPathologic featuresInterstitial fibrosisFibroblast accumulationNephropathyMouse model