2014
Systems Immunology Reveals Markers of Susceptibility to West Nile Virus Infection
Qian F, Goel G, Meng H, Wang X, You F, Devine L, Raddassi K, Garcia MN, Murray KO, Bolen CR, Gaujoux R, Shen-Orr SS, Hafler D, Fikrig E, Xavier R, Kleinstein SH, Montgomery RR. Systems Immunology Reveals Markers of Susceptibility to West Nile Virus Infection. MSphere 2014, 22: 6-16. PMID: 25355795, PMCID: PMC4278927, DOI: 10.1128/cvi.00508-14.Peer-Reviewed Original ResearchConceptsWest Nile virus infectionVirus infectionMyeloid dendritic cellsMarker of susceptibilityPotential therapeutic strategySeverity of infectionSevere neurological diseaseOlder patientsAcute infectionDendritic cellsCXCL10 expressionDetectable yearsImmunity-related genesStratified cohortWNV infectionTherapeutic strategiesPathogenic mechanismsAnimal studiesNeurological diseasesDisease severityVivo infectionPredictive signatureInfectionProminent alterationsPrimary cells
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 ResearchMeSH KeywordsAdultDisease ResistanceFemaleGene Expression ProfilingGene Knockdown TechniquesHigh-Throughput Nucleotide SequencingHumansMacrophagesMaleRNAWest Nile virusYoung AdultConceptsCommon 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 infectionThe lipoprotein La7 contributes to Borrelia burgdorferi persistence in ticks and their transmission to naïve hosts
Yang X, Hegde S, Shroder DY, Smith AA, Promnares K, Neelakanta G, Anderson JF, Fikrig E, Pal U. The lipoprotein La7 contributes to Borrelia burgdorferi persistence in ticks and their transmission to naïve hosts. Microbes And Infection 2013, 15: 729-737. PMID: 23774694, PMCID: PMC3769513, DOI: 10.1016/j.micinf.2013.06.001.Peer-Reviewed Original ResearchConceptsComplex enzootic cycleInner membrane proteinB. burgdorferi persistenceProtein-protein interactionsOuter membrane lipoproteinNaïve hostsSpirochete life cycleCo-immunoprecipitation studiesMammalian infectivityMembrane proteinsRedundant rolesMolecular detailsMammalian hostsMembrane lipoproteinGene expressionWild typeInfection cycleLiquid chromatography-mass spectrometry analysisPathogen survivalBiological significanceHost transmissionEnzootic cyclePathogen transmissionSpectrometry analysisLA7
2012
Ixodes scapularis JAK-STAT Pathway Regulates Tick Antimicrobial Peptides, Thereby Controlling the Agent of Human Granulocytic Anaplasmosis
Liu L, Dai J, Zhao YO, Narasimhan S, Yang Y, Zhang L, Fikrig E. Ixodes scapularis JAK-STAT Pathway Regulates Tick Antimicrobial Peptides, Thereby Controlling the Agent of Human Granulocytic Anaplasmosis. The Journal Of Infectious Diseases 2012, 206: 1233-1241. PMID: 22859824, PMCID: PMC3448968, DOI: 10.1093/infdis/jis484.Peer-Reviewed Original ResearchConceptsJAK-STAT pathwayTick salivary glandsA. phagocytophilum infectionAntimicrobial peptidesElectrophoretic mobility shift assaysPeptide-encoding genesMobility shift assaysPhagocytophilum infectionHuman granulocytic anaplasmosisGene familyTransducer activatorMammalian hostsRNA interferenceShift assaysTranscription pathwayGene expressionJAK-STATJanus kinaseGranulocytic anaplasmosisSalivary glandsPathwayGenesCritical roleAnaplasma phagocytophilumKey roleActivation of the RpoN-RpoS regulatory pathway during the enzootic life cycle of Borrelia burgdorferi
Ouyang Z, Narasimhan S, Neelakanta G, Kumar M, Pal U, Fikrig E, Norgard MV. Activation of the RpoN-RpoS regulatory pathway during the enzootic life cycle of Borrelia burgdorferi. BMC Microbiology 2012, 12: 44. PMID: 22443136, PMCID: PMC3320556, DOI: 10.1186/1471-2180-12-44.Peer-Reviewed Original ResearchConceptsRpoN-RpoS regulatory pathwayRpoN-RpoS pathwayExpression of rpoSEnzootic life cycleMammalian infectionRegulatory pathwaysTranscription of rpoSOuter membrane lipoproteinLife cycleB. burgdorferiKey environmental stimuliLyme disease pathogenesisDiverse nichesMembrane lipoproteinMammalian hostsTarget genesTranscription levelsMicrobial survivalLipoprotein geneRpoSOrganism adaptationInfectious cycleFed larvaeIntermolt larvaeSustained transcriptionPostgenomic Analyses Reveal Development of Infectious Anaplasma phagocytophilum during Transmission from Ticks to Mice
Mastronunzio JE, Kurscheid S, Fikrig E. Postgenomic Analyses Reveal Development of Infectious Anaplasma phagocytophilum during Transmission from Ticks to Mice. Journal Of Bacteriology 2012, 194: 2238-2247. PMID: 22389475, PMCID: PMC3347074, DOI: 10.1128/jb.06791-11.Peer-Reviewed Original ResearchConceptsOpen reading frameA. phagocytophilum genomeObligate intracellular bacteriaBlood-feeding arthropodsCell surface proteinsMammalian cell cultureRickettsiales orderUncharacterized proteinsRibosomal proteinsEssential proteinsTranscriptome sequencingBacterial adaptationA. phagocytophilumDNA replicationTick salivary glandsPostgenomic analysisReading frameMammalian hostsAnaplasma phagocytophilumDevelopmental transitionsDC-specific markerIntracellular bacteriaTransmission feedingSurface proteinsProtein
2011
Alterations in the Aedes aegypti Transcriptome during Infection with West Nile, Dengue and Yellow Fever Viruses
Colpitts TM, Cox J, Vanlandingham DL, Feitosa FM, Cheng G, Kurscheid S, Wang P, Krishnan MN, Higgs S, Fikrig E. Alterations in the Aedes aegypti Transcriptome during Infection with West Nile, Dengue and Yellow Fever Viruses. PLOS Pathogens 2011, 7: e1002189. PMID: 21909258, PMCID: PMC3164632, DOI: 10.1371/journal.ppat.1002189.Peer-Reviewed Original ResearchConceptsGene expressionDiverse cellular processesPupal cuticle proteinsExpression of genesMosquito gene expressionYellow fever virusFlaviviral infectionsMosquito genesCuticle proteinsCellular processesBioinformatics analysisMosquito cellsExpression profilesMicroarray analysisDDR genesMetabolic processesHuman diseasesGenesTranscriptomic signaturesWest NileFever virusPeptidase activityWNV envelope proteinTranscriptomeAedes aegypti mosquitoes
2009
Toll-Like Receptors 1 and 2 Heterodimers Alter Borrelia burgdorferi Gene Expression in Mice and Ticks
Fikrig E, Narasimhan S, Neelakanta G, Pal U, Chen M, Flavell R. Toll-Like Receptors 1 and 2 Heterodimers Alter Borrelia burgdorferi Gene Expression in Mice and Ticks. The Journal Of Infectious Diseases 2009, 200: 1331-1340. PMID: 19754309, PMCID: PMC2846271, DOI: 10.1086/605950.Peer-Reviewed Original ResearchConceptsGene expressionMicroarray analysisB. burgdorferi gene expressionQuantitative reverse transcription-polymerase chain reaction analysisToll-like receptor 1Reverse transcription-polymerase chain reaction analysisReceptor 1Expression profilesWild-type animalsHost TLRsArthropod vectorsMessenger RNA levelsPolymerase chain reaction analysisChain reaction analysisB. burgdorferi-infected ticksGenesBurgdorferi-infected ticksRNA levelsExpressionMurine hostBorrelia burgdorferiReaction analysisWild-type miceAnimalsHeterodimers
2008
RNA interference screen for human genes associated with West Nile virus infection
Krishnan MN, Ng A, Sukumaran B, Gilfoy FD, Uchil PD, Sultana H, Brass AL, Adametz R, Tsui M, Qian F, Montgomery RR, Lev S, Mason PW, Koski RA, Elledge SJ, Xavier RJ, Agaisse H, Fikrig E. RNA interference screen for human genes associated with West Nile virus infection. Nature 2008, 455: 242-245. PMID: 18690214, PMCID: PMC3136529, DOI: 10.1038/nature07207.Peer-Reviewed Original ResearchMeSH KeywordsComputational BiologyDengue VirusEndoplasmic ReticulumGene Expression ProfilingGenome, HumanHeLa CellsHIVHumansImmunityMonocarboxylic Acid TransportersMuscle ProteinsProtein BindingRNA InterferenceUbiquitinationUbiquitin-Protein LigasesVesiculovirusVirus ReplicationWest Nile FeverWest Nile virusA Differential Role for BB0365 in the Persistence of Borrelia burgdorferi in Mice and Ticks
Pal U, Dai J, Li X, Neelakanta G, Luo P, Kumar M, Wang P, Yang X, Anderson JF, Fikrig E. A Differential Role for BB0365 in the Persistence of Borrelia burgdorferi in Mice and Ticks. The Journal Of Infectious Diseases 2008, 197: 148-155. PMID: 18171298, DOI: 10.1086/523764.Peer-Reviewed Original ResearchConceptsVertebrate hostsWild-type B. burgdorferiArthropod vectorsB. burgdorferi persistenceB. burgdorferi transcriptomeDiverse murine tissuesSpirochete life cycleLife cycleB. burgdorferi B31Lyme disease agentGene productsMurine tissuesGenesWild rodentsDisease agentsDifferential rolesFeeding ticksB. burgdorferiInfectious isolatesHostBorrelia burgdorferiTicksTranscriptomePersistence of BorreliaMutants
2005
Early Transcriptional Response of Human Neutrophils to Anaplasma phagocytophilum Infection
Sukumaran B, Carlyon JA, Cai JL, Berliner N, Fikrig E. Early Transcriptional Response of Human Neutrophils to Anaplasma phagocytophilum Infection. Infection And Immunity 2005, 73: 8089-8099. PMID: 16299303, PMCID: PMC1307096, DOI: 10.1128/iai.73.12.8089-8099.2005.Peer-Reviewed Original ResearchConceptsEarly transcriptional responseTranscriptional responseGene expressionHost cell gene expressionComprehensive DNA microarray analysisA. phagocytophilum infectionDNA microarray analysisObligate intracellular pathogensCell gene expressionCFLAR geneTNFSF10 geneA. phagocytophilum-infected neutrophilsCytoskeletal remodelingVesicular transportTranscriptional profilesHost pathwaysMicroarray analysisAntiapoptotic genesPromyelocytic cell lineDifferential expressionPhagocytophilum infectionHost cellsGenesHuman neutrophilsIntracellular pathogens
2002
Repression of rac2 mRNA Expression by Anaplasma phagocytophila Is Essential to the Inhibition of Superoxide Production and Bacterial Proliferation
Carlyon JA, Chan WT, Galán J, Roos D, Fikrig E. Repression of rac2 mRNA Expression by Anaplasma phagocytophila Is Essential to the Inhibition of Superoxide Production and Bacterial Proliferation. The Journal Of Immunology 2002, 169: 7009-7018. PMID: 12471136, DOI: 10.4049/jimmunol.169.12.7009.Peer-Reviewed Original ResearchConceptsInfected HL-60 cellsHL-60 cellsAnaplasma phagocytophilaMRNA expressionNADPH oxidaseRetinoic acid-differentiated HL-60 cellsBacterial intracellular survivalHuman granulocytic ehrlichiosisNADPH oxidase activityNADPH oxidase activationQuantitative RT-PCRCMV immediate-early promoterInfected neutrophilsEtiologic agentGranulocytic ehrlichiosisRT-PCR analysisA. phagocytophilaIntracellular survivalSuperoxide productionOxidase activationNeutrophilsProtein expressionRT-PCRImmediate early promoterH postinfectionMolecular Adaptation of Borrelia burgdorferi in the Murine Host
Liang FT, Nelson FK, Fikrig E. Molecular Adaptation of Borrelia burgdorferi in the Murine Host. Journal Of Experimental Medicine 2002, 196: 275-280. PMID: 12119353, PMCID: PMC2193918, DOI: 10.1084/jem.20020770.Peer-Reviewed Original ResearchConceptsLipoprotein geneMolecular adaptationsHost immune selection pressureAnalysis of expressionNovel adaptation mechanismSteps of adaptationSelection pressureLyme disease spirocheteB. burgdorferiMurine hostGenesHost tissuesImmune selection pressureAdaptation mechanismsChronic infectionMurine infectionCritical stepHostBorrelia burgdorferiInfectionAdaptationSpirochetesBurgdorferiInitial inoculumPathogens