2024
UBR5 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 load
2021
A critical role for MSR1 in vesicular stomatitis virus infection of the central nervous system
Yang D, Lin T, Li C, Harrison A, Geng T, Wang P. A critical role for MSR1 in vesicular stomatitis virus infection of the central nervous system. IScience 2021, 24: 102678. PMID: 34169243, PMCID: PMC8208900, DOI: 10.1016/j.isci.2021.102678.Peer-Reviewed Original ResearchMacrophage scavenger receptor 1Vesicular stomatitis virus infectionCentral nervous systemStomatitis virus infectionSpinal cordVirus infectionNervous systemLethal VSV infectionMsr1 deficient miceM2 macrophage polarizationWild-type miceInnate immune responseReceptor-dependent mannerScavenger receptor 1Cellular entryViral loadReduced morbidityImmune responseMacrophage polarizationVSV infectionMSR1 expressionViral pathogenesisReceptor 1Bacterial infectionsHost defense
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
2019
The 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 expression
2018
Zika Virus Non-structural Protein 4A Blocks the RLR-MAVS Signaling
Ma J, Ketkar H, Geng T, Lo E, Wang L, Xi J, Sun Q, Zhu Z, Cui Y, Yang L, Wang P. Zika Virus Non-structural Protein 4A Blocks the RLR-MAVS Signaling. Frontiers In Microbiology 2018, 9: 1350. PMID: 29988497, PMCID: PMC6026624, DOI: 10.3389/fmicb.2018.01350.Peer-Reviewed Original ResearchMelanoma differentiation-associated protein 5Zika virusImmune responseNon-structural protein 4AReceptor-mediated immune responsesToll-like receptor-mediated immune responsesRe-emerging flavivirusGuillain-Barre syndromeAntiviral immune responseType I interferon inductionHost immune systemI interferon inductionMammalian host immune systemProtein 4AN-terminal caspase activationMolecular mechanismsNeonatal microcephalyZIKV pathogenesisZIKV replicationImmune evasionImmune systemHuman trophoblastsReceptor signalingSubsequent inductionProtein 5UBXN3B positively regulates STING-mediated antiviral immune responses
Yang L, Wang L, Ketkar H, Ma J, Yang G, Cui S, Geng T, Mordue DG, Fujimoto T, Cheng G, You F, Lin R, Fikrig E, Wang P. UBXN3B positively regulates STING-mediated antiviral immune responses. Nature Communications 2018, 9: 2329. PMID: 29899553, PMCID: PMC5998066, DOI: 10.1038/s41467-018-04759-8.Peer-Reviewed Original ResearchConceptsUbiquitin regulatory X domain-containing proteinAntiviral immune responseImmune responseDeficient immune responseDomain-containing proteinsInterferon genes (STING) signalingVesicular stomatitis virus infectionDiverse biological processesStomatitis virus infectionPhosphorylation of TBK1Physiological evidenceHerpes simplex virus 1Cre-loxP approachSimplex virus 1Virus infectionAdult miceGene signalingHSV-1Biological processesPhysiological functionsVirus 1MicePrimary cellsConsequent recruitmentResponse
2017
An essential role of PI3K in the control of West Nile virus infection
Wang L, Yang L, Fikrig E, Wang P. An essential role of PI3K in the control of West Nile virus infection. Scientific Reports 2017, 7: 3724. PMID: 28623344, PMCID: PMC5473900, DOI: 10.1038/s41598-017-03912-5.Peer-Reviewed Original ResearchConceptsWest Nile virus infectionPI3K inhibitorsPI3KVirus infectionImmune responseK inhibitorsType I IFN responseAntiviral immune responseI IFN responseCatalytic subunit p110δTNF-α protein productionPrimary mouse macrophagesFlaviviral infectionsAntiviral immunityIFN responseViral titersClass I PI3KAntiviral roleMRNA expressionPI3K activityIFNProtein expressionInfectionMouse macrophagesCell proliferation
2016
Exploration of West Nile Virus Infection in Mouse Models
Wang P. Exploration of West Nile Virus Infection in Mouse Models. Methods In Molecular Biology 2016, 1435: 71-81. PMID: 27188551, DOI: 10.1007/978-1-4939-3670-0_7.Peer-Reviewed Original ResearchConceptsWest Nile virusMouse modelWest Nile virus infectionExperimental mouse modelAntiviral immune responseCentral nervous systemWNV pathogenesisLeukocyte numbersVirus infectionImmune responseBlood leukocytesWNV infectionNervous systemNeurological diseasesMouse brainViral titersResidential cellsLeukocytesNile virusVirus spreadInfectionImmunopathologyPathogenesisCNSDisease
2013
UBXN1 Interferes with Rig-I-like Receptor-Mediated Antiviral Immune Response by Targeting MAVS
Wang P, Yang L, Cheng G, Yang G, Xu Z, You F, Sun Q, Lin R, Fikrig E, Sutton RE. UBXN1 Interferes with Rig-I-like Receptor-Mediated Antiviral Immune Response by Targeting MAVS. Cell Reports 2013, 3: 1057-1070. PMID: 23545497, PMCID: PMC3707122, DOI: 10.1016/j.celrep.2013.02.027.Peer-Reviewed Original ResearchConceptsAntiviral immune responseInnate immune responseImmune responseLike receptorsSystemic antiviral immune responsesVirus-induced innate immune responsesDengue virus infectionType I interferon responseI interferon responseRNA virusesVirus infectionViral infectionStrong inhibitory effectViral replicationVirus replicationInterferon responseRNA virus replicationInhibitory effectWest NileMAVSVesicular stomatitisInfectionAdaptor moleculeFamily membersReceptors
2009
The Urokinase Receptor (uPAR) Facilitates Clearance of Borrelia burgdorferi
Hovius JW, Bijlsma MF, van der Windt GJ, Wiersinga WJ, Boukens BJ, Coumou J, Oei A, de Beer R, de Vos AF, van 't Veer C, van Dam AP, Wang P, Fikrig E, Levi MM, Roelofs JJ, van der Poll T. The Urokinase Receptor (uPAR) Facilitates Clearance of Borrelia burgdorferi. PLOS Pathogens 2009, 5: e1000447. PMID: 19461880, PMCID: PMC2678258, DOI: 10.1371/journal.ppat.1000447.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArthritis, InfectiousBorrelia burgdorferiCell MovementHeartHistocytochemistryHumansLeukocytesLyme DiseaseMiceMice, Inbred C57BLMice, KnockoutMyocarditisPhagocytosisReceptors, Urokinase Plasminogen ActivatorSkinStatistics, NonparametricUp-RegulationUrinary BladderUrokinase-Type Plasminogen ActivatorConceptsB. burgdorferi numbersWT controlsPhagocytotic capacityC3H/HeN backgroundIL-1beta mRNA expressionBorrelia burgdorferiB. burgdorferi infectionRole of uPARSevere carditisBurgdorferi infectionImmune responseLeukocyte functionSpirochete Borrelia burgdorferiFibrinolytic systemPAI-1Facilitate clearanceMRNA expressionHuman leukocytesLyme borreliosisMiceB. burgdorferiCausative agentProteinase receptorUPARAdequate eradication