2021
Aedes aegypti SNAP and a calcium transporter ATPase influence dengue virus dissemination
Marin-Lopez A, Jiang J, Wang Y, Cao Y, MacNeil T, Hastings AK, Fikrig E. Aedes aegypti SNAP and a calcium transporter ATPase influence dengue virus dissemination. PLOS Neglected Tropical Diseases 2021, 15: e0009442. PMID: 34115766, PMCID: PMC8195420, DOI: 10.1371/journal.pntd.0009442.Peer-Reviewed Original ResearchConceptsSalivary gland proteinsSuccessful viral transmissionNew mammalian hostDengue virusWild habitatsHabitat expansionGland proteinsA. aegypti vectorMammalian hostsUbiquitous expressionDENV infectionGene expressionMosquito midgutProtein componentsATPase proteinVector proteinProteinSalivary glandsBlood mealViral cycleAedes aegypti mosquitoesSusceptible hostsAedes aegyptiMosquitoesHost
2018
A potent prolyl tRNA synthetase inhibitor antagonizes Chikungunya and Dengue viruses
Hwang J, Jiang A, Fikrig E. A potent prolyl tRNA synthetase inhibitor antagonizes Chikungunya and Dengue viruses. Antiviral Research 2018, 161: 163-168. PMID: 30521835, PMCID: PMC6345585, DOI: 10.1016/j.antiviral.2018.11.017.Peer-Reviewed Original ResearchConceptsDengue virusSignificant morbiditySafe vaccineSynthetase inhibitionEndemic areasSynthetase inhibitorFlavivirus genusMosquito-bornePotent antagonistHost factorsGroup of pathogensVirusMultiple virusesChikungunyaHematophagous arthropod vectorsAedes sppArthropod vectorsEpidemic pathogensAdditional approachesMorbidityPathogensVaccineAntagonistMortalityHuman population
2016
Zika virus infection of Hofbauer cells
Simoni MK, Jurado KA, Abrahams VM, Fikrig E, Guller S. Zika virus infection of Hofbauer cells. American Journal Of Reproductive Immunology 2016, 77 PMID: 27966815, PMCID: PMC5299062, DOI: 10.1111/aji.12613.Peer-Reviewed Original ResearchConceptsCongenital Zika syndromeHofbauer cellsZika virusZIKV infectionDevelopment of CZSDengue virusSpread of ZIKVVertical transmissionFetal placental macrophagesPlacental Hofbauer cellsZika virus infectionAntenatal infectionNeonatal outcomesPlacental responsesZika syndromeVirus infectionCurrent evidenceCongenital abnormalitiesRecent studiesNeonatal developmentFetal capillariesRelated flavivirusesInfectionSpecific molecular mechanismsCertain virusesAedes aegypti D7 Saliva Protein Inhibits Dengue Virus Infection
Conway MJ, Londono-Renteria B, Troupin A, Watson AM, Klimstra WB, Fikrig E, Colpitts TM. Aedes aegypti D7 Saliva Protein Inhibits Dengue Virus Infection. PLOS Neglected Tropical Diseases 2016, 10: e0004941. PMID: 27632170, PMCID: PMC5025043, DOI: 10.1371/journal.pntd.0004941.Peer-Reviewed Original ResearchConceptsSalivary gland extractsDengue virus infectionD7 proteinDengue virus type 1Virus type 1DENV envelope proteinAegypti salivaLymph nodesDENV infectionDENV virionsVirus infectionRelevant arbovirusesType 1InfectionHost skinBlood feedingEnvelope proteinNovel roleBinding assaysSalivaAedes aegyptiGland extractsPrimary vectorHPLC fractionsFeedingA novel mosquito ubiquitin targets viral envelope protein for degradation and reduces virion production during dengue virus infection
Troupin A, Londono-Renteria B, Conway MJ, Cloherty E, Jameson S, Higgs S, Vanlandingham DL, Fikrig E, Colpitts TM. A novel mosquito ubiquitin targets viral envelope protein for degradation and reduces virion production during dengue virus infection. Biochimica Et Biophysica Acta 2016, 1860: 1898-1909. PMID: 27241849, PMCID: PMC4949077, DOI: 10.1016/j.bbagen.2016.05.033.Peer-Reviewed Original ResearchConceptsProtein degradationUbiquitin proteinGene expressionProtein expression constructsSite-directed mutagenesisViral protein degradationInnate immune signalingDengue virusProteasomal degradationProtein interactionsExpression constructsMosquito cellsSignificant human diseaseMicroarray analysisImmune signalingViral envelope proteinsVirus infectionHuman diseasesBlood feedingAmino acidsProteinMultiple functionsQRT-PCRVirion productionAntiviral function
2015
Dengue Virus Infection of Aedes aegypti Requires a Putative Cysteine Rich Venom Protein
Londono-Renteria B, Troupin A, Conway MJ, Vesely D, Ledizet M, Roundy CM, Cloherty E, Jameson S, Vanlandingham D, Higgs S, Fikrig E, Colpitts TM. Dengue Virus Infection of Aedes aegypti Requires a Putative Cysteine Rich Venom Protein. PLOS Pathogens 2015, 11: e1005202. PMID: 26491875, PMCID: PMC4619585, DOI: 10.1371/journal.ppat.1005202.Peer-Reviewed Original ResearchConceptsDENV infectionVirus infectionDengue virusCysteine-rich venom proteinsSpecific antiviral therapyDengue virus infectionMosquito-borne flavivirusAedes aegypti cellsAntiviral therapyFlavivirus infectionMultiple flavivirusesTherapeutic measuresNew treatmentsAedes aegyptiInfectionGene targetsSerious human diseasesAegypti cellsMosquito vectorsVaccineVenom proteinsFlavivirusesHuman diseasesMosquitoesAntiserum inhibits
2013
Mosquito Saliva Serine Protease Enhances Dissemination of Dengue Virus into the Mammalian Host
Conway MJ, Watson AM, Colpitts TM, Dragovic SM, Li Z, Wang P, Feitosa F, Shepherd DT, Ryman KD, Klimstra WB, Anderson JF, Fikrig E. Mosquito Saliva Serine Protease Enhances Dissemination of Dengue Virus into the Mammalian Host. Journal Of Virology 2013, 88: 164-175. PMID: 24131723, PMCID: PMC3911723, DOI: 10.1128/jvi.02235-13.Peer-Reviewed Original ResearchConceptsDengue virusDENV infectivityAedes aegypti salivaMurine lymph nodesSalivary gland extractsAegypti salivaPrevention of diseaseLymph nodesMosquito salivaDENV loadVivo modelSerine protease activityNovel targetViral attachmentViral infectivityVirus infectivitySerine protease inhibitorHeparan sulfate proteoglycanExtracellular matrix proteinsRNA knockdownProtease inhibitorsInfectivitySulfate proteoglycanCell migrationMammalian hosts
2012
Antibodies against the Envelope Glycoprotein Promote Infectivity of Immature Dengue Virus Serotype 2
da Silva Voorham JM, Rodenhuis-Zybert IA, Nuñez N, Colpitts TM, van der Ende-Metselaar H, Fikrig E, Diamond MS, Wilschut J, Smit JM. Antibodies against the Envelope Glycoprotein Promote Infectivity of Immature Dengue Virus Serotype 2. PLOS ONE 2012, 7: e29957. PMID: 22431958, PMCID: PMC3303773, DOI: 10.1371/journal.pone.0029957.Peer-Reviewed Original ResearchConceptsAntibody-dependent enhancementImmature DENVAnti-prM antibodiesStructural proteins prMSevere dengue diseaseDengue virus antibodiesDengue virus serotype 2Dose-dependent mannerImmature particlesStandard virus preparationsVirus preparationsVirus antibodiesPrecursor membrane proteinVirus serotype 2Lethal infectionMouse modelDengue diseaseImmune serumDENV particlesProtein prMInfection studiesAntibodiesEnhanced infectivityInfectionSerotype 2
2011
Dengue Virus Capsid Protein Binds Core Histones and Inhibits Nucleosome Formation in Human Liver Cells
Colpitts TM, Barthel S, Wang P, Fikrig E. Dengue Virus Capsid Protein Binds Core Histones and Inhibits Nucleosome Formation in Human Liver Cells. PLOS ONE 2011, 6: e24365. PMID: 21909430, PMCID: PMC3164731, DOI: 10.1371/journal.pone.0024365.Peer-Reviewed Original ResearchConceptsDENV infectionDENV CHuman liver cellsDengue virusLiver cellsDengue virus infectionTime-dependent mannerSpecific antiviralsVirus infectionInfectionAlters levelsSerious human diseasesInteresting new roleViral RNANuclear presenceMature virus particlesVirus particlesHuman diseasesFlaviviral replicationCellsCellular responsesCapsid proteinStructural proteinsVaccineAlterations 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 mosquitoesAn In Vivo Transfection Approach Elucidates a Role for Aedes aegypti Thioester-Containing Proteins in Flaviviral Infection
Cheng G, Liu L, Wang P, Zhang Y, Zhao YO, Colpitts TM, Feitosa F, Anderson JF, Fikrig E. An In Vivo Transfection Approach Elucidates a Role for Aedes aegypti Thioester-Containing Proteins in Flaviviral Infection. PLOS ONE 2011, 6: e22786. PMID: 21818390, PMCID: PMC3144946, DOI: 10.1371/journal.pone.0022786.Peer-Reviewed Original ResearchUse of a tandem affinity purification assay to detect interactions between West Nile and dengue viral proteins and proteins of the mosquito vector
Colpitts TM, Cox J, Nguyen A, Feitosa F, Krishnan MN, Fikrig E. Use of a tandem affinity purification assay to detect interactions between West Nile and dengue viral proteins and proteins of the mosquito vector. Virology 2011, 417: 179-187. PMID: 21700306, PMCID: PMC3166580, DOI: 10.1016/j.virol.2011.06.002.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCadherinsCulicidaeDengue VirusInsect ProteinsInsect VectorsProtein BindingViral ProteinsWest Nile virusConceptsWest Nile virus infectionWest NileMosquito vectorsWest Nile virus envelope proteinMosquito proteinsSignificant morbidityFlavivirus infectionDengue viral proteinsVirus envelope proteinVirus infectionMosquito factorsDengue virusNovel targetInfectionMosquito cellsDengueEnvelope proteinMyosin light chain kinaseViral proteinsFlavivirusesLight chain kinasePI3-kinaseChain kinaseNS2B proteinCells
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 pathogensFusion 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 diseasesEffective siRNA targeting of the 3′ untranslated region of the West Nile virus genome
Anthony KG, Bai F, Krishnan MN, Fikrig E, Koski RA. Effective siRNA targeting of the 3′ untranslated region of the West Nile virus genome. Antiviral Research 2009, 82: 166-168. PMID: 19135091, DOI: 10.1016/j.antiviral.2008.12.007.Peer-Reviewed Original ResearchConceptsWest Nile virusSiRNA targetsSpecific antiviral therapyRelated dengue virusAntiviral therapyWNV pathogenesisShort hairpin RNA sequencesDengue virusWNV replicationTherapeutic potentialViral replicationRNA interferenceAntiviral therapeuticsSiRNA targetingPotential antiviral therapeuticsVero cellsNile virusSequence-specific inhibitorsHuman pathogensUntranslated regionVirusVirus genomeWest Nile virus genomeTargetPathogenesis
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 virus
2007
Rab 5 Is Required for the Cellular Entry of Dengue and West Nile Viruses
Krishnan MN, Sukumaran B, Pal U, Agaisse H, Murray JL, Hodge TW, Fikrig E. Rab 5 Is Required for the Cellular Entry of Dengue and West Nile Viruses. Journal Of Virology 2007, 81: 4881-4885. PMID: 17301152, PMCID: PMC1900185, DOI: 10.1128/jvi.02210-06.Peer-Reviewed Original Research
2006
Crystal Structure of West Nile Virus Envelope Glycoprotein Reveals Viral Surface Epitopes
Kanai R, Kar K, Anthony K, Gould LH, Ledizet M, Fikrig E, Marasco WA, Koski RA, Modis Y. Crystal Structure of West Nile Virus Envelope Glycoprotein Reveals Viral Surface Epitopes. Journal Of Virology 2006, 80: 11000-11008. PMID: 16943291, PMCID: PMC1642136, DOI: 10.1128/jvi.01735-06.Peer-Reviewed Original ResearchConceptsWest Nile virus-specific antibodiesEnvelope glycoproteinTick-borne encephalitis virusWest Nile Virus Envelope GlycoproteinLife-threatening encephalitisVirus-specific antibodiesWest Nile virusMajor envelope glycoproteinAntiviral vaccinesVirus envelope glycoproteinDengue virusEncephalitis virusFlavivirus genusViral attachmentReceptor bindingWest NileTherapeutic antibodiesMolecular landscapeNile virusVirusSurface epitopesE proteinViruses e.Viral surfaceVirus surface