2020
Single cell immune profiling of dengue virus patients reveals intact immune responses to Zika virus with enrichment of innate immune signatures
Zhao Y, Amodio M, Vander Wyk B, Gerritsen B, Kumar MM, van Dijk D, Moon K, Wang X, Malawista A, Richards MM, Cahill ME, Desai A, Sivadasan J, Venkataswamy MM, Ravi V, Fikrig E, Kumar P, Kleinstein SH, Krishnaswamy S, Montgomery RR. Single cell immune profiling of dengue virus patients reveals intact immune responses to Zika virus with enrichment of innate immune signatures. PLOS Neglected Tropical Diseases 2020, 14: e0008112. PMID: 32150565, PMCID: PMC7082063, DOI: 10.1371/journal.pntd.0008112.Peer-Reviewed Original ResearchConceptsZika virusCell subsetsDengue virusConcurrent dengue infectionInnate cell responsesInnate immune signaturesVirus-infected individualsDivergent clinical outcomesMosquito-borne human pathogenIntact immune responsePre-existing infectionInnate cell typesSingle-cell immune profilingPublic health importanceCell typesImmune signaturesVirus patientsWest Nile virusAcute patientsClinical outcomesImmune profilingDengue infectionImmune statusFunctional statusImmune cells
2019
AgBR1 antibodies delay lethal Aedes aegypti-borne West Nile virus infection in mice
Uraki R, Hastings AK, Brackney DE, Armstrong PM, Fikrig E. AgBR1 antibodies delay lethal Aedes aegypti-borne West Nile virus infection in mice. Npj Vaccines 2019, 4: 23. PMID: 31312526, PMCID: PMC6614468, DOI: 10.1038/s41541-019-0120-x.Peer-Reviewed Original ResearchWest Nile virus infectionWest Nile virusVirus infectionInfected Aedes aegypti mosquitoesZika virus pathogenesisMosquito salivary proteinsViral loadAedes aegypti mosquitoesLethal infectionVirus pathogenesisSevere diseaseInfectionNile virusAegypti mosquitoesMiceAntibodiesSalivary proteinsMosquitoesMeningoencephalitisPathogenesisAgBR1Disease
2018
Small Interfering RNA-Mediated Control of Virus Replication in the CNS Is Therapeutic and Enables Natural Immunity to West Nile Virus
Beloor J, Maes N, Ullah I, Uchil P, Jackson A, Fikrig E, Lee SK, Kumar P. Small Interfering RNA-Mediated Control of Virus Replication in the CNS Is Therapeutic and Enables Natural Immunity to West Nile Virus. Cell Host & Microbe 2018, 23: 549-556.e3. PMID: 29606496, PMCID: PMC6074029, DOI: 10.1016/j.chom.2018.03.001.Peer-Reviewed Original ResearchConceptsWest Nile virusWNV infectionCell-mediated immune responsesLate-stage therapySubsequent WNV infectionWNV-infected miceLong-term immunityNile virusWNV E proteinViral burdenIntranasal routeVirus clearanceVirus infectionImmune responseMice succumbPeripheral tissuesNatural immunitySurvival rateDisease resultsDay 9Virus replicationInfectionImmunityCNSVirus
2017
Zika Virus and Sexual Transmission: A New Route of Transmission for Mosquito-borne Flaviviruses.
Hastings AK, Fikrig E. Zika Virus and Sexual Transmission: A New Route of Transmission for Mosquito-borne Flaviviruses. The Yale Journal Of Biology And Medicine 2017, 90: 325-330. PMID: 28656018, PMCID: PMC5482308.Peer-Reviewed Original ResearchConceptsSexual transmissionZika virusWorld Health OrganizationWest Nile virusAcute onset paralysisUnprotected sexual contactRoutes of transmissionNew global epidemicSevere birth defectsBody achesMild feverAnimal modelsInfected mosquitoesVaginal secretionsViral infectionMain mosquito vectorGlobal epidemicFlaviviridae familyImportant human pathogenSexual contactDisease controlHealth OrganizationZika transmissionNile virusBirth defects
2016
TLR8 Couples SOCS-1 and Restrains TLR7-Mediated Antiviral Immunity, Exacerbating West Nile Virus Infection in Mice
Paul AM, Acharya D, Le L, Wang P, Stokic DS, Leis AA, Alexopoulou L, Town T, Flavell RA, Fikrig E, Bai F. TLR8 Couples SOCS-1 and Restrains TLR7-Mediated Antiviral Immunity, Exacerbating West Nile Virus Infection in Mice. The Journal Of Immunology 2016, 197: 4425-4435. PMID: 27798161, PMCID: PMC5123688, DOI: 10.4049/jimmunol.1600902.Peer-Reviewed Original ResearchConceptsWest Nile virusAntiviral immunityWNV infectionWest Nile virus infectionOverexpression of TLR7Induced IFNsWild-type controlsSuppressor of cytokineTLR7 expressionNeuronal deathVirus infectionHuman TLR7TLR7TLR8InfectionMiceX proteinReduced expressionImmunityNile virusSOCS-1RNA knockdownIFNNovel roleProapoptotic genes
2014
Immune Markers Associated with Host Susceptibility to Infection with West Nile Virus
Qian F, Thakar J, Yuan X, Nolan M, Murray KO, Lee WT, Wong SJ, Meng H, Fikrig E, Kleinstein SH, Montgomery RR. Immune Markers Associated with Host Susceptibility to Infection with West Nile Virus. Viral Immunology 2014, 27: 39-47. PMID: 24605787, PMCID: PMC3949440, DOI: 10.1089/vim.2013.0074.Peer-Reviewed Original ResearchConceptsWest Nile virusSevere infectionsImmune markersIL-4IL-4 levelsSerum cytokine levelsSerum IL-4Nile virusSignificant risk factorsImmune system statusPeripheral blood cellsSevere neurological diseaseCytokine levelsAntibody levelsImmune statusRisk factorsHealthy subjectsStratified cohortWNV infectionNeurological diseasesInfectionAltered expression levelsBlood cellsAltered gene expression patternsHost susceptibility
2013
Identification of Genes Critical for Resistance to Infection by West Nile Virus Using RNA-Seq Analysis
Qian F, Chung L, Zheng W, Bruno V, Alexander RP, Wang Z, Wang X, Kurscheid S, Zhao H, Fikrig E, Gerstein M, Snyder M, Montgomery RR. Identification of Genes Critical for Resistance to Infection by West Nile Virus Using RNA-Seq Analysis. Viruses 2013, 5: 1664-1681. PMID: 23881275, PMCID: PMC3738954, DOI: 10.3390/v5071664.Peer-Reviewed Original ResearchConceptsCommon gene pathwaysNovel cellular responsesDifferential gene expressionRNA-seq analysisWest Nile virusGene expression analysisPrimary human macrophagesGene isoformsHigh-throughput methodRNA-seqGene pathwaysExpression analysisGenes CriticalKnock-downGene expressionCellular responsesGene changesResistant individualsBiological settingsHuman macrophagesGenesCritical roleAvailable treatmentsHealthy donorsViral infection
2012
West Nile Virus: Biology, Transmission, and Human Infection
Colpitts TM, Conway MJ, Montgomery RR, Fikrig E. West Nile Virus: Biology, Transmission, and Human Infection. Clinical Microbiology Reviews 2012, 25: 635-648. PMID: 23034323, PMCID: PMC3485754, DOI: 10.1128/cmr.00045-12.Peer-Reviewed Original ResearchHumoral immune responses in humanized BLT mice immunized with West Nile virus and HIV‐1 envelope proteins are largely mediated via human CD5+ B cells
Biswas S, Chang H, Sarkis P, Fikrig E, Zhu Q, Marasco W. Humoral immune responses in humanized BLT mice immunized with West Nile virus and HIV‐1 envelope proteins are largely mediated via human CD5+ B cells. Immunology 2012, 136: 361-361. PMCID: PMC3385036, DOI: 10.1111/j.1365-2567.2012.03586.x.Peer-Reviewed Original ResearchHorizontal and Vertical Transmission of West Nile Virus Genotype NY99 by Culex salinarius and Genotypes NY99 and WN02 by Culex tarsalis
Anderson JF, Main AJ, Cheng G, Ferrandino FJ, Fikrig E. Horizontal and Vertical Transmission of West Nile Virus Genotype NY99 by Culex salinarius and Genotypes NY99 and WN02 by Culex tarsalis. American Journal Of Tropical Medicine And Hygiene 2012, 86: 134-139. PMID: 22232464, PMCID: PMC3247122, DOI: 10.4269/ajtmh.2012.11-0473.Peer-Reviewed Original Research
2011
Innate immune control of West Nile virus infection
Arjona A, Wang P, Montgomery RR, Fikrig E. Innate immune control of West Nile virus infection. Cellular Microbiology 2011, 13: 1648-1658. PMID: 21790942, PMCID: PMC3196381, DOI: 10.1111/j.1462-5822.2011.01649.x.Peer-Reviewed Original ResearchConceptsWest Nile virusWNV infectionAntiviral innate immune mechanismsLong-term neurologic sequelaeWest Nile virus infectionRe-emerging zoonotic pathogenInnate immune controlInnate immune mechanismsLife-threatening meningoencephalitisInnate immune systemNeurologic sequelaeImmune controlInflammatory mediatorsImmune mechanismsMammalian hostsVirus infectionCurrent evidenceViral infectionAntiviral effectorsImmune systemFlaviviridae familyAntiviral mechanismInfectionNile virusJAK-STATprM-antibody renders immature West Nile virus infectious in vivo
Colpitts TM, Rodenhuis-Zybert I, Moesker B, Wang P, Fikrig E, Smit JM. prM-antibody renders immature West Nile virus infectious in vivo. Journal Of General Virology 2011, 92: 2281-2285. PMID: 21697345, PMCID: PMC3347797, DOI: 10.1099/vir.0.031427-0.Peer-Reviewed Original ResearchConceptsWest Nile virusInfectious West Nile virusNile virusDeath of micePrM antibodiesNeurotropic pathogensWNV particlesSevere human diseasesFamily FlaviviridaeVivo proofImmature flavivirus particlesInfectious potentialAntibodiesDiseaseViral surfaceVirus particlesPrM proteinFlavivirus particlesVirusHuman diseasesInfectionMiceFlavivirusesBrainSerumImpaired Interferon Signaling in Dendritic Cells From Older Donors Infected In Vitro With West Nile Virus
Qian F, Wang X, Zhang L, Lin A, Zhao H, Fikrig E, Montgomery RR. Impaired Interferon Signaling in Dendritic Cells From Older Donors Infected In Vitro With West Nile Virus. The Journal Of Infectious Diseases 2011, 203: 1415-1424. PMID: 21398396, PMCID: PMC3080893, DOI: 10.1093/infdis/jir048.Peer-Reviewed Original ResearchConceptsDendritic cellsWest Nile virusOlder donorsAntiviral responseToll-like receptor 3Initial antiviral responseLate-phase responseNile virusSignificant age-related differencesSignificant human morbidityType I IFNQuantified cytokinesRNA flavivirusAge-related differencesYoung donorsI IFNReceptor RIGViral infectionReceptor 3Human morbidityOlder populationCritical regulatory pathwaysInterferon SignalingNuclear translocationDefective regulation
2010
A Paradoxical Role for Neutrophils in the Pathogenesis of West Nile Virus
Bai F, Kong KF, Dai J, Qian F, Zhang L, Brown CR, Fikrig E, Montgometry R. A Paradoxical Role for Neutrophils in the Pathogenesis of West Nile Virus. The Journal Of Infectious Diseases 2010, 202: 1804-1812. PMID: 21050124, PMCID: PMC3053000, DOI: 10.1086/657416.Peer-Reviewed Original ResearchConceptsWest Nile virusPolymorphonuclear leukocytesWNV infectionNile virusHigh viremiaViral clearanceEarly deathEarly infectionControl groupProtective roleBiphasic responseInnate immunityViral pathogenesisInfectionMiceViremiaPathogenesisParadoxical roleEfficient replicationVirusCXCL1CXCL2ChemokinesCXCR2NeutrophilsCaspase-12 controls West Nile virus infection via the viral RNA receptor RIG-I
Wang P, Arjona A, Zhang Y, Sultana H, Dai J, Yang L, LeBlanc PM, Doiron K, Saleh M, Fikrig E. Caspase-12 controls West Nile virus infection via the viral RNA receptor RIG-I. Nature Immunology 2010, 11: 912-919. PMID: 20818395, PMCID: PMC3712356, DOI: 10.1038/ni.1933.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCaspase 12Cells, CulturedDEAD Box Protein 58DEAD-box RNA HelicasesDNA-Binding ProteinsFibroblastsImmunity, InnateInterferon Type IMiceMice, Inbred C57BLMice, KnockoutNeuronsReceptors, VirusSignal TransductionTranscription FactorsUbiquitinationUbiquitin-Protein LigasesWest Nile FeverWest Nile virusA C-Type Lectin Collaborates with a CD45 Phosphatase Homolog to Facilitate West Nile Virus Infection of Mosquitoes
Cheng G, Cox J, Wang P, Krishnan MN, Dai J, Qian F, Anderson JF, Fikrig E. A C-Type Lectin Collaborates with a CD45 Phosphatase Homolog to Facilitate West Nile Virus Infection of Mosquitoes. Cell 2010, 142: 714-725. PMID: 20797779, PMCID: PMC2954371, DOI: 10.1016/j.cell.2010.07.038.Peer-Reviewed Original ResearchConceptsWest Nile virusWNV infectionWest Nile virus infectionArthropod-borne flavivirusBlood-feeding processVirus infectionHuman CD45Viral disseminationC-type lectinInfectionViral entryViral attachmentMosquito homologCalcium-dependent mannerNile virusMolecular understandingVivo experimentsSame pathwayNatural vectorTLR9-Targeted Biodegradable Nanoparticles as Immunization Vectors Protect against West Nile Encephalitis
Demento SL, Bonafé N, Cui W, Kaech SM, Caplan MJ, Fikrig E, Ledizet M, Fahmy TM. TLR9-Targeted Biodegradable Nanoparticles as Immunization Vectors Protect against West Nile Encephalitis. The Journal Of Immunology 2010, 185: 2989-2997. PMID: 20660705, PMCID: PMC3753007, DOI: 10.4049/jimmunol.1000768.Peer-Reviewed Original ResearchConceptsBiodegradable nanoparticlesUnmodified nanoparticlesImmune responseNanoparticlesCell-mediated immune responsesRobust humoral responseTh1 immune responseEffector T cellsAg-specific lymphocytesTh2-biased responsesAdjuvant aluminum hydroxideWest Nile encephalitisVirus encephalitisWest Nile virusAgHumoral responseCpG oligodeoxynucleotideT cellsMouse modelLive virusInfectious agentsProtein AgVaccine developmentWN virusNile virus
2009
The IFITM Proteins Mediate Cellular Resistance to Influenza A H1N1 Virus, West Nile Virus, and Dengue Virus
Brass AL, Huang IC, Benita Y, John SP, Krishnan MN, Feeley EM, Ryan BJ, Weyer JL, van der Weyden L, Fikrig E, Adams DJ, Xavier RJ, Farzan M, Elledge SJ. The IFITM Proteins Mediate Cellular Resistance to Influenza A H1N1 Virus, West Nile Virus, and Dengue Virus. Cell 2009, 139: 1243-1254. PMID: 20064371, PMCID: PMC2824905, DOI: 10.1016/j.cell.2009.12.017.Peer-Reviewed Original ResearchConceptsAntiviral restriction factorsWest Nile virusDengue virusInfluenza A H1N1 virusesNile virusRestriction factorsInterferon type ICellular innate immunityH1N1 virusRespiratory illnessMajor human pathogenViral infectionInnate immunityViral replicationIFITM proteinsInfluenza virusInfluenzaHost cell machineryVirusIFITMsInfectionEndosomal acidificationCellular resistanceType IHuman pathogensIL-10 Signaling Blockade Controls Murine West Nile Virus Infection
Bai F, Town T, Qian F, Wang P, Kamanaka M, Connolly TM, Gate D, Montgomery RR, Flavell RA, Fikrig E. IL-10 Signaling Blockade Controls Murine West Nile Virus Infection. PLOS Pathogens 2009, 5: e1000610. PMID: 19816558, PMCID: PMC2749443, DOI: 10.1371/journal.ppat.1000610.Peer-Reviewed Original ResearchConceptsIL-10 signalingIL-10WNV infectionWest Nile virusIL-10-deficient miceWest Nile virus infectionImportant cellular sourceSignificant human morbidityRNA flavivirusWNV pathogenesisInterleukin-10Antiviral cytokinesEtiologic rolePharmacologic blockadeDeficient miceT cellsVirus infectionPharmacologic meansTherapeutic strategiesViral infectionCellular sourceInfectionHuman morbidityNile virusMiceFusion Loop Peptide of the West Nile Virus Envelope Protein Is Essential for Pathogenesis and Is Recognized by a Therapeutic Cross-Reactive Human Monoclonal Antibody
Sultana H, Foellmer HG, Neelakanta G, Oliphant T, Engle M, Ledizet M, Krishnan MN, Bonafé N, Anthony KG, Marasco WA, Kaplan P, Montgomery RR, Diamond MS, Koski RA, Fikrig E. Fusion Loop Peptide of the West Nile Virus Envelope Protein Is Essential for Pathogenesis and Is Recognized by a Therapeutic Cross-Reactive Human Monoclonal Antibody. The Journal Of Immunology 2009, 183: 650-660. PMID: 19535627, PMCID: PMC3690769, DOI: 10.4049/jimmunol.0900093.Peer-Reviewed Original ResearchConceptsWest Nile virus envelope proteinWest Nile virusVirus envelope proteinDengue virusCross-reactive human monoclonal antibodiesBlood-brain barrier permeabilityEnvelope proteinWest Nile virus infectionNeutralization escape variantsNile virusWest Nile encephalitisNeutralization escape mutantsHuman monoclonal antibodyFatal neurological diseaseParental West Nile virusFusion loopEscape variantsInflammatory responseBarrier permeabilityLethal encephalitisMAb11Virus infectionHuman mAbsEscape mutantsNeurological diseases