2024
Autoregulated 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 complexA 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 infectionProteinNS4AUBR5 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: e55671. PMID: 36197120, PMCID: PMC9638853, DOI: 10.15252/embr.202255671.Peer-Reviewed Original ResearchLipases 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 modelA mutation-mediated evolutionary adaptation of Zika virus in mosquito and mammalian host
Yu X, Shan C, Zhu Y, Ma E, Wang J, Wang P, Shi P, Cheng G. A mutation-mediated evolutionary adaptation of Zika virus in mosquito and mammalian host. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2113015118. PMID: 34620704, PMCID: PMC8545446, DOI: 10.1073/pnas.2113015118.Peer-Reviewed Original ResearchConceptsEvolutionary adaptationZIKV capsid proteinAsian ZIKV lineageZika virusMammalian hostsZIKV mutantsNS2B-NS3 proteaseStructural proteinsPreferred substrateHuman cellsCapsid proteinInfectious viral particlesMutantsMosquito vectorsZIKV disseminationMillions of infectionsZIKV lineagesProteinViral particlesHigh prevalenceImmunodeficient miceMosquito infectionExplosive outbreaksMosquitoesStable substitutionsPharmacological Inhibition of STAT6 Ameliorates Myeloid Fibroblast Activation and Alternative Macrophage Polarization in Renal Fibrosis
Jiao B, An C, Tran M, Du H, Wang P, Zhou D, Wang Y. Pharmacological Inhibition of STAT6 Ameliorates Myeloid Fibroblast Activation and Alternative Macrophage Polarization in Renal Fibrosis. Frontiers In Immunology 2021, 12: 735014. PMID: 34512669, PMCID: PMC8426438, DOI: 10.3389/fimmu.2021.735014.Peer-Reviewed Original ResearchConceptsChronic kidney diseaseFolic acid administrationUnilateral ureteral obstructionRenal fibrosisM2 macrophage polarizationMacrophage polarizationUreteral obstructionFibroblast activationAcid administrationKidney functionKidney diseaseKidney fibrosisPreserves kidney functionSTAT6 activationVehicle-treated miceFolic acid nephropathyExperimental murine modelAlternative macrophage polarizationWild-type miceNovel therapeutic approachesExtracellular matrix protein productionSTAT6 inhibitorMatrix protein productionAS1517499Effective therapyUBX Domain Protein 6 Positively Regulates JAK-STAT1/2 Signaling.
Ketkar H, Harrison A, Graziano V, Geng T, Yang L, Vella A, Wang P. UBX Domain Protein 6 Positively Regulates JAK-STAT1/2 Signaling. The Journal Of Immunology 2021, 206: 2682-2691. PMID: 34021047, PMCID: PMC8164993, DOI: 10.4049/jimmunol.1901337.Peer-Reviewed Original ResearchConceptsTyrosine kinase 2Domain-containing proteinsExpression of hundredsComplex cellular regulationRNA viral replicationJAK/STATCellular regulationType I/III IFNsKinase 2JAK/Type I/III IFNProtein 6IFN expressionGenesViral infectionSignalingExpressionViral replicationExpression of IFNCellsType IProteinSTATOverexpressionDeletionInteraction of Viruses with the Insect Intestine
Ma E, Zhu Y, Liu Z, Wei T, Wang P, Cheng G. Interaction of Viruses with the Insect Intestine. Annual Review Of Virology 2021, 8: 1-17. PMID: 33872516, DOI: 10.1146/annurev-virology-091919-100543.Peer-Reviewed Original ResearchConceptsSymbiotic microorganismsCell-intrinsic antiviral immunityIntrinsic antiviral immunityInsect's intestinal tractVirus-encoded componentsInsect herbivoresFoliage feedingInsect intestineHematophagous insectsPeritrophic matrixIntestinal tractInsectsBlood feedingInteraction of virusVirus invasionIntricate roleAntiviral immunityViral invasionMicroorganismsConstant threatImmunological barrierInvasionUnderlying mechanismHerbivoresNutritional statusGlucose-mediated proliferation of a gut commensal bacterium promotes Plasmodium infection by increasing mosquito midgut pH
Wang M, An Y, Gao L, Dong S, Zhou X, Feng Y, Wang P, Dimopoulos G, Tang H, Wang J. Glucose-mediated proliferation of a gut commensal bacterium promotes Plasmodium infection by increasing mosquito midgut pH. Cell Reports 2021, 35: 108992. PMID: 33882310, PMCID: PMC8116483, DOI: 10.1016/j.celrep.2021.108992.Peer-Reviewed Original ResearchConceptsPlasmodium infectionGlucose metabolismMalaria parasitesCommensal bacteriumMosquito midgutPlasmodium berghei infectionGut commensal bacteriumBerghei infectionMosquito-microbiota interactionsDietary glucoseInfectionMetabolome changesVector competencePlasmodium gametogenesisVector competencyGlucoseImportant determinantPlasmodiumProliferationMetabolismMosquitoesParasitesAsaia bogorensis
2020
A Critical Role for STING Signaling in Limiting Pathogenesis of Chikungunya Virus
Geng T, Lin T, Yang D, Harrison AG, Vella AT, Fikrig E, Wang P. A Critical Role for STING Signaling in Limiting Pathogenesis of Chikungunya Virus. The Journal Of Infectious Diseases 2020, 223: 2186-2196. PMID: 33161431, PMCID: PMC8205639, DOI: 10.1093/infdis/jiaa694.Peer-Reviewed Original ResearchConceptsVirus infectionSTING signalingGt miceType I IFN responseChikungunya virus infectionImmune cell infiltrationWild-type miceActivator of neutrophilsInnate immune responseExpression of interferonI IFN responseExpression of chemoattractantsRNA virus infectionDNA virus infectionInterferon genes (STING) pathwayCHIKV arthritisViremic stageArthritis progressionViral burdenArthritis pathogenesisChemokine responsesCell infiltrationJoint damageImmune responseSTING deficiencyCXCL10 Signaling Contributes to the Pathogenesis of Arthritogenic Alphaviruses
Lin T, Geng T, Harrison AG, Yang D, Vella AT, Fikrig E, Wang P. CXCL10 Signaling Contributes to the Pathogenesis of Arthritogenic Alphaviruses. Viruses 2020, 12: 1252. PMID: 33147869, PMCID: PMC7692144, DOI: 10.3390/v12111252.Peer-Reviewed Original ResearchConceptsChikungunya virusAlphaviral arthritisArthritogenic alphavirusesLargest immune cell populationMacrophages/T cellsImmune cell populationsInflammatory immune responseLow viral loadWild-type miceO'nyong-nyong virusWild-type animalsRheumatic manifestationsImmune infiltratesViral loadT cellsImmune responseAlphaviral diseaseArthritic diseasesTherapeutic targetCXCL10PathogenesisViral RNACell populationsArthritisFootpad