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 ResearchAutoregulated 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 complexAn 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 ResearchA 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 ResearchA 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 substitutions
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 populationsArthritisFootpadMacrophage scavenger receptor 1 controls Chikungunya virus infection through autophagy in mice
Yang L, Geng T, Yang G, Ma J, Wang L, Ketkar H, Yang D, Lin T, Hwang J, Zhu S, Wang Y, Dai J, You F, Cheng G, Vella AT, Flavell RA, Fikrig E, Wang P. Macrophage scavenger receptor 1 controls Chikungunya virus infection through autophagy in mice. Communications Biology 2020, 3: 556. PMID: 33033362, PMCID: PMC7545163, DOI: 10.1038/s42003-020-01285-6.Peer-Reviewed Original ResearchConceptsMacrophage scavenger receptor 1Scavenger receptor 1Chikungunya virusReceptor 1Antiviral roleType I IFN responseChikungunya virus infectionLow-density lipoproteinImportant antiviral roleI IFN responseMarkers of autophagyCHIKV infectionViral loadArthritogenic alphavirusesVirus infectionCHIKV replicationATG5-ATG12Antiviral actionKnockout miceMSR1 expressionIFN responseInfectionMiceNsp1 proteinAutophagic functionA mosquito salivary protein promotes flavivirus transmission by activation of autophagy
Sun P, Nie K, Zhu Y, Liu Y, Wu P, Liu Z, Du S, Fan H, Chen CH, Zhang R, Wang P, Cheng G. A mosquito salivary protein promotes flavivirus transmission by activation of autophagy. Nature Communications 2020, 11: 260. PMID: 31937766, PMCID: PMC6959235, DOI: 10.1038/s41467-019-14115-z.Peer-Reviewed Original ResearchConceptsBeclin-1Viral transmissionFlavivirus transmissionMosquito salivary proteinsHost immune cellsZika virus transmissionActivation of autophagyLow viremiaProphylactic targetsMosquito salivaImmune cellsZIKV transmissionAllergen 1Infected mosquitoesViral infectionMonocyte lineageVirus transmissionMiceMosquitoesSalivary proteinsNumerous studiesViremiaInfectionFlavivirusesProtein
2019
Host serum iron modulates dengue virus acquisition by mosquitoes
Zhu Y, Tong L, Nie K, Wiwatanaratanabutr I, Sun P, Li Q, Yu X, Wu P, Wu T, Yu C, Liu Q, Bian Z, Wang P, Cheng G. Host serum iron modulates dengue virus acquisition by mosquitoes. Nature Microbiology 2019, 4: 2405-2415. PMID: 31527795, DOI: 10.1038/s41564-019-0555-x.Peer-Reviewed Original ResearchConceptsSerum ironDengue virusVirus acquisitionDengue virus infectionIron-deficient miceDengue virus prevalenceIron metabolism pathwaysViral loadIron supplementationA. aegypti mosquitoesHigh prevalenceVirus infectionArbovirus infectionHuman donorsIron deficiencyInfectionBlood componentsGut epitheliumReactive oxygen speciesSusceptibility of mosquitoesVirus prevalenceAegypti mosquitoesBlood mealHuman bloodVirusThe Nuclear Matrix Protein SAFA Surveils Viral RNA and Facilitates Immunity by Activating Antiviral Enhancers and Super-enhancers
Cao L, Liu S, Li Y, Yang G, Luo Y, Li S, Du H, Zhao Y, Wang D, Chen J, Zhang Z, Li M, Ouyang S, Gao X, Sun Y, Wang Z, Yang L, Lin R, Wang P, You F. The Nuclear Matrix Protein SAFA Surveils Viral RNA and Facilitates Immunity by Activating Antiviral Enhancers and Super-enhancers. Cell Host & Microbe 2019, 26: 369-384.e8. PMID: 31513772, DOI: 10.1016/j.chom.2019.08.010.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphatasesAnimalsAntiviral AgentsChromosomal Proteins, Non-HistoneDNA Topoisomerases, Type IDNA VirusesHEK293 CellsHeLa CellsHerpesvirus 1, HumanHeterogeneous-Nuclear Ribonucleoprotein UHost-Pathogen InteractionsHumansImmunity, InnateInterferon Regulatory Factor-3Interferon Regulatory Factor-7MiceNuclear Matrix-Associated ProteinsProtein Serine-Threonine KinasesReceptors, Pattern RecognitionRNA VirusesRNA, Double-StrandedRNA, ViralVirusesConceptsImmune gene transcriptionViral RNAViral RNA sensorsChromatin remodelingTrigger innate immune responsesSuper enhancersGene transcriptionExtranuclear localizationRNA virusesInnate immune responseAntiviral genesDsRNA sensorsRNA sensorsViral dsRNAAntiviral stateAntiviral responseType I IFNDsRNAVSV infectionRobust antiviral responseRNAEnhancerI IFNImmune responseHSV-1The GRA15 protein from Toxoplasma gondii enhances host defense responses by activating the interferon stimulator STING
Wang P, Li S, Zhao Y, Zhang B, Li Y, Liu S, Du H, Cao L, Ou M, Ye X, Li P, Gao X, Wang P, Jing C, Shao F, Yang G, You F. The GRA15 protein from Toxoplasma gondii enhances host defense responses by activating the interferon stimulator STING. Journal Of Biological Chemistry 2019, 294: 16494-16508. PMID: 31416833, PMCID: PMC6851339, DOI: 10.1074/jbc.ra119.009172.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDisease Models, AnimalHEK293 CellsHumansImmunity, InnateInterferon-gammaInterleukin-12 Subunit p35Membrane ProteinsMiceMice, Inbred C57BLMice, KnockoutNucleotidyltransferasesProtein MultimerizationProtozoan ProteinsSpleenSurvival RateToxoplasmaToxoplasmosisTumor Necrosis Factor Receptor-Associated Peptides and ProteinsUbiquitinationConceptsImmune responseCyclic GMP-AMP synthaseWT miceRobust innate immune responseCGAS-deficient miceHost immune responseInnate immune responseType I IFNCGAS/STING signalingInterferon-stimulated genesGMP-AMP synthaseInflammatory cytokinesNeurotropic pathogensGRA15Mouse modelSevere symptomsI IFNLatent infectionSTING signalingHigh mortalityMiceInfectionHost defense responsesStingsHost cellsEndogenous Retrovirus-Derived Long Noncoding RNA Enhances Innate Immune Responses via Derepressing RELA Expression
Zhou B, Qi F, Wu F, Nie H, Song Y, Shao L, Han J, Wu Z, Saiyin H, Wei G, Wang P, Ni T, Qian F. Endogenous Retrovirus-Derived Long Noncoding RNA Enhances Innate Immune Responses via Derepressing RELA Expression. MBio 2019, 10: 10.1128/mbio.00937-19. PMID: 31363026, PMCID: PMC6667616, DOI: 10.1128/mbio.00937-19.Peer-Reviewed Original ResearchConceptsAntiviral immune responseImmune responseInnate immune responseNF-κB subunitsExpression of RelADeficient miceI interferonAntiviral responseVirus-induced cytokine productionHost genome instabilityEndogenous retrovirusesNF-κB signalingType I interferonRNA virus infectionViral RNA mimicViral loadCytokine productionViral challengeVirus infectionLong noncoding RNADeleterious roleRelA expressionViral replicationViral sensorsReduced expressionLack of efficacy of ivermectin for prevention of a lethal Zika virus infection in a murine system
Ketkar H, Yang L, Wormser GP, Wang P. Lack of efficacy of ivermectin for prevention of a lethal Zika virus infection in a murine system. Diagnostic Microbiology And Infectious Disease 2019, 95: 38-40. PMID: 31097261, PMCID: PMC6697611, DOI: 10.1016/j.diagmicrobio.2019.03.012.Peer-Reviewed Original ResearchConceptsZika virus infectionAnti-Zika virus activityVirus infectionAnimal modelsZika virusLethal Zika Virus InfectionIFNAR1 knockout miceZika virus strainLack of efficacyEffectiveness of ivermectinLethal infectionKnockout miceVirus activityAntiviral activityMurine systemVirus strainsDrug ivermectinInfectionIvermectinStudy limitationsPreventionVirusSenegal strainMiceGenetic Determinants of the Re-Emergence of Arboviral Diseases
Ketkar H, Herman D, Wang P. Genetic Determinants of the Re-Emergence of Arboviral Diseases. Viruses 2019, 11: 150. PMID: 30759739, PMCID: PMC6410223, DOI: 10.3390/v11020150.Peer-Reviewed Original ResearchConceptsViral genetic determinantsPublic health threatGenetic determinantsZika virusViral transmissionInfectious diseasesArboviral diseasesWest NileHealth threatYellow feverDiseaseViral fitnessViral geneticsVector competenceInternational travelVirusMosquitoesGlobal climate changeMosquito populationsFeverHost