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 complex
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 loadMosquito-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 ResearchA 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 antibodiesLipases 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 infection
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 substitutionsUBX 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 IProteinSTATOverexpressionDeletion
2020
Mechanisms of SARS-CoV-2 Transmission and Pathogenesis
Harrison AG, Lin T, Wang P. Mechanisms of SARS-CoV-2 Transmission and Pathogenesis. Trends In Immunology 2020, 41: 1100-1115. PMID: 33132005, PMCID: PMC7556779, DOI: 10.1016/j.it.2020.10.004.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Severe acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Coronavirus infectious disease 2019Respiratory syndrome coronavirus 2SARS-CoV-2 transmissionTissue tropismSyndrome coronavirus 2SARS-CoV-2 researchBroad tissue tropismCoronavirus 2Pathogenic coronavirusesDisease 2019Immune antagonismTherapeutic testingAnimal modelsViral pathogenesisVaccine developmentPathogenesisTropismFuture investigationsHuman populationMacrophage 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
Progress towards Understanding the Mosquito-Borne Virus Life Cycle
Yu X, Zhu Y, Xiao X, Wang P, Cheng G. Progress towards Understanding the Mosquito-Borne Virus Life Cycle. Trends In Parasitology 2019, 35: 1009-1017. PMID: 31669148, DOI: 10.1016/j.pt.2019.09.006.Peer-Reviewed Original ResearchHost 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-1Chikungunya Virus and (Re-) Emerging Alphaviruses
Wang P, Zhang R. Chikungunya Virus and (Re-) Emerging Alphaviruses. Viruses 2019, 11: 779. PMID: 31450552, PMCID: PMC6784149, DOI: 10.3390/v11090779.Peer-Reviewed Original ResearchThe 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 expressionIdentification of genetic variations in Necator americanus through resequencing by whole genome amplification
Liu Y, Liu H, Xie Y, Zhang B, Zou X, Ou M, Ye X, Han Y, Wu J, Chen X, Dong S, Zhu K, Guo C, Wang P, Zhai H, Jing C, Yang G. Identification of genetic variations in Necator americanus through resequencing by whole genome amplification. Journal Of International Medical Research 2019, 47: 4353-4364. PMID: 31331217, PMCID: PMC6753555, DOI: 10.1177/0300060519862069.Peer-Reviewed Original ResearchConceptsWhole-genome resequencingSingle nucleotide polymorphismsGenome resequencingGenetic variationParasite genome sequencesDe novo genome assemblyMost single nucleotide polymorphismsGene ontology analysisNovo genome assemblyMultiple displacement amplification (MDA) methodCommon drug targetsWhole genome amplificationGenome assemblyOntology analysisReference genomeGenome sequenceGO analysisSequencing readsDrug targetsGenome amplificationSmall parasitesNucleotide polymorphismsParasite samplesGenotype probabilitiesResequencing