2024
High burden of viruses and bacterial pathobionts drives heightened nasal innate immunity in children
Watkins T, Green A, Amat J, Cheemarla N, Hänsel K, Lozano R, Dudgeon S, Germain G, Landry M, Schulz W, Foxman E. High burden of viruses and bacterial pathobionts drives heightened nasal innate immunity in children. Journal Of Experimental Medicine 2024, 221: e20230911. PMID: 38949638, PMCID: PMC11215523, DOI: 10.1084/jem.20230911.Peer-Reviewed Original ResearchConceptsBacterial pathobiontsRespiratory virusesBurden of virusesSARS-CoV-2Innate immune activationSARS-CoV-2 viral loadDynamic host-pathogen interactionsInnate immune responseViral coinfectionCytokine profileViral loadNasal virusImmune activationProinflammatory responseIL-1BNasopharyngeal samplesHost-pathogen interactionsImmune responseInterferon responsePathobiontsInnate immunityPaired samplesCXCL10Healthy 1-year-oldVirus
2023
Double-take: SARS-CoV-2 has evolved to evade human innate immunity, twice
Foxman E. Double-take: SARS-CoV-2 has evolved to evade human innate immunity, twice. Trends In Immunology 2023, 45: 1-3. PMID: 38143224, DOI: 10.1016/j.it.2023.12.001.Peer-Reviewed Original ResearchPLSCR1 is a cell-autonomous defence factor against SARS-CoV-2 infection
Xu D, Jiang W, Wu L, Gaudet R, Park E, Su M, Cheppali S, Cheemarla N, Kumar P, Uchil P, Grover J, Foxman E, Brown C, Stansfeld P, Bewersdorf J, Mothes W, Karatekin E, Wilen C, MacMicking J. PLSCR1 is a cell-autonomous defence factor against SARS-CoV-2 infection. Nature 2023, 619: 819-827. PMID: 37438530, PMCID: PMC10371867, DOI: 10.1038/s41586-023-06322-y.Peer-Reviewed Original ResearchConceptsC-terminal β-barrel domainSpike-mediated fusionCell-autonomous defenseLarge-scale exome sequencingΒ-barrel domainGenome-wide CRISPRSARS-CoV-2 infectionHost cell cytosolScramblase activityPhospholipid scramblaseLive SARS-CoV-2 infectionHuman lung epitheliumPLSCR1SARS-CoV-2 USASingle-molecule switchingSARS-CoV-2 variantsExome sequencingHuman populationRestriction factorsViral RNANew SARS-CoV-2 variantsSARS-CoV-2Robust activityLung epitheliumDefense factorsRespiratory viruses: New frontiers—a Keystone Symposia report
Cable J, Sun J, Cheon I, Vaughan A, Castro I, Stein S, López C, Gostic K, Openshaw P, Ellebedy A, Wack A, Hutchinson E, Thomas M, Langlois R, Lingwood D, Baker S, Folkins M, Foxman E, Ward A, Schwemmle M, Russell A, Chiu C, Ganti K, Subbarao K, Sheahan T, Penaloza‐MacMaster P, Eddens T. Respiratory viruses: New frontiers—a Keystone Symposia report. Annals Of The New York Academy Of Sciences 2023, 1522: 60-73. PMID: 36722473, PMCID: PMC10580159, DOI: 10.1111/nyas.14958.Peer-Reviewed Original ResearchConceptsRespiratory virusesSARS-CoV-2Specific viral strainsMechanisms of diseaseAcute infectionChronic diseasesCommon causeEffective treatmentNovel treatmentsVirus-host interactionsPrevention strategiesTherapy efficacyViral strainsVulnerable populationsPrevention approachesVirusDiseaseSymposium reportTreatmentViral biologyMorbidityPopulationInfectionMortalityInfluenzaNasal host response-based screening for undiagnosed respiratory viruses: a pathogen surveillance and detection study
Cheemarla N, Hanron A, Fauver J, Bishai J, Watkins T, Brito A, Zhao D, Alpert T, Vogels C, Ko A, Schulz W, Landry M, Grubaugh N, van Dijk D, Foxman E. Nasal host response-based screening for undiagnosed respiratory viruses: a pathogen surveillance and detection study. The Lancet Microbe 2023, 4: e38-e46. PMID: 36586415, PMCID: PMC9835789, DOI: 10.1016/s2666-5247(22)00296-8.Peer-Reviewed Original ResearchConceptsRespiratory virus panelPg/mLCXCL10 concentrationsSARS-CoV-2Bacterial pathobiontsRespiratory virusesSARS-CoV-2 negative samplesViral respiratory infectionsSARS-CoV-2 positive samplesClinical virology laboratoryHealth care systemVirus-positive samplesQuantitative RT-PCRInfluenza C virusSymptomatic patientsRespiratory infectionsSeasonal coronavirusesNasopharyngeal swabsVirus panelC virusCommon virusesCXCL10Host responseInterferon responseVirology laboratory
2021
Dynamic innate immune response determines susceptibility to SARS-CoV-2 infection and early replication kinetics
Cheemarla NR, Watkins TA, Mihaylova VT, Wang B, Zhao D, Wang G, Landry ML, Foxman EF. Dynamic innate immune response determines susceptibility to SARS-CoV-2 infection and early replication kinetics. Journal Of Experimental Medicine 2021, 218: e20210583. PMID: 34128960, PMCID: PMC8210587, DOI: 10.1084/jem.20210583.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAngiotensin-Converting Enzyme 2Case-Control StudiesChemokine CXCL10COVID-19Disease SusceptibilityFemaleGene Expression ProfilingHost-Pathogen InteractionsHumansImmunity, InnateInterferonsMaleMiddle AgedNasopharynxPicornaviridae InfectionsSARS-CoV-2Viral LoadVirus ReplicationConceptsSARS-CoV-2 infectionSARS-CoV-2 exposureSARS-CoV-2Interferon-stimulated genesUpper respiratory tractRespiratory tractEarly SARS-CoV-2 infectionDynamic innate immune responseViral replicationSARS-CoV-2 replicationPatient nasopharyngeal samplesInnate immune responseLow infectious doseViral loadNasopharyngeal samplesImmune responseInfectious doseISG responseAntiviral responseInfection progressionViral transmissionLevel correlatesInfectionISG inductionInitial replicationSingle-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes
Ravindra NG, Alfajaro MM, Gasque V, Huston NC, Wan H, Szigeti-Buck K, Yasumoto Y, Greaney AM, Habet V, Chow RD, Chen JS, Wei J, Filler RB, Wang B, Wang G, Niklason LE, Montgomery RR, Eisenbarth SC, Chen S, Williams A, Iwasaki A, Horvath TL, Foxman EF, Pierce RW, Pyle AM, van Dijk D, Wilen CB. Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes. PLOS Biology 2021, 19: e3001143. PMID: 33730024, PMCID: PMC8007021, DOI: 10.1371/journal.pbio.3001143.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionSARS-CoV-2Human bronchial epithelial cellsInterferon-stimulated genesCell state changesAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionSyndrome coronavirus 2 infectionCell tropismCoronavirus 2 infectionCoronavirus disease 2019Onset of infectionCell-intrinsic expressionCourse of infectionAir-liquid interface culturesHost-viral interactionsBronchial epithelial cellsSingle-cell RNA sequencingCell typesIL-1Disease 2019Human airwaysDevelopment of therapeuticsDrug AdministrationViral replicationViral interference cannot be concluded from datasets containing only symptomatic patients – Authors' reply
Wu A, Mihaylova VT, Landry ML, Foxman EF. Viral interference cannot be concluded from datasets containing only symptomatic patients – Authors' reply. The Lancet Microbe 2021, 2: e10. PMID: 35544223, DOI: 10.1016/s2666-5247(20)30218-4.Peer-Reviewed Original ResearchHumansViral Interference
2020
Interference between rhinovirus and influenza A virus: a clinical data analysis and experimental infection study
Wu A, Mihaylova VT, Landry ML, Foxman EF. Interference between rhinovirus and influenza A virus: a clinical data analysis and experimental infection study. The Lancet Microbe 2020, 1: e254-e262. PMID: 33103132, PMCID: PMC7580833, DOI: 10.1016/s2666-5247(20)30114-2.Peer-Reviewed Original ResearchConceptsRhinovirus infectionInterferon-stimulated genesExperimental infection studiesClinical data analysisMock infectionInfection studiesDay 3ISG expressionViral interferenceInterferon responsePrimary human airway epithelial culturesYale-New Haven HospitalHuman airway epithelial culturesIAV RNASeasonal influenza epidemicsNational InstituteAirway epithelial culturesReverse transcription-quantitative PCRTranscription-quantitative PCRElectronic medical record systemPeak virusAirway mucosaMedical record systemRespiratory virusesIAV infectionAnalytical sensitivity and efficiency comparisons of SARS-CoV-2 RT–qPCR primer–probe sets
Vogels CBF, Brito AF, Wyllie AL, Fauver JR, Ott IM, Kalinich CC, Petrone ME, Casanovas-Massana A, Catherine Muenker M, Moore AJ, Klein J, Lu P, Lu-Culligan A, Jiang X, Kim DJ, Kudo E, Mao T, Moriyama M, Oh JE, Park A, Silva J, Song E, Takahashi T, Taura M, Tokuyama M, Venkataraman A, Weizman OE, Wong P, Yang Y, Cheemarla NR, White EB, Lapidus S, Earnest R, Geng B, Vijayakumar P, Odio C, Fournier J, Bermejo S, Farhadian S, Dela Cruz CS, Iwasaki A, Ko AI, Landry ML, Foxman EF, Grubaugh ND. Analytical sensitivity and efficiency comparisons of SARS-CoV-2 RT–qPCR primer–probe sets. Nature Microbiology 2020, 5: 1299-1305. PMID: 32651556, PMCID: PMC9241364, DOI: 10.1038/s41564-020-0761-6.Peer-Reviewed Original ResearchConceptsSARS-CoV-2SARS-CoV-2 RTSevere acute respiratory syndrome coronavirusAcute respiratory syndrome coronavirusViral RNA copiesPublic health laboratoriesPublic health interventionsReverse transcription-PCR assaySARS-CoV-2 diagnostic testingDiagnostic assaysTranscription-PCR assaySARS-CoV-2 evolutionQuantitative reverse transcription-PCR assaysRapid diagnostic assaysHealth laboratoriesHealth interventionsDiagnostic testingRNA copiesPrimer-probe setsAssaysLow sensitivityCritical needAnalytical sensitivityPoly(I:C) causes failure of immunoprophylaxis to red blood cells expressing the KEL glycoprotein in mice
Escamilla-Rivera V, Liu J, Gibb DR, Santhanakrishnan M, Liu D, Forsmo JE, Eisenbarth S, Foxman EF, Stowell SR, Luckey CJ, Zimring JC, Hudson KE, Hendrickson J. Poly(I:C) causes failure of immunoprophylaxis to red blood cells expressing the KEL glycoprotein in mice. Blood 2020, 135: 1983-1993. PMID: 32266378, PMCID: PMC7256361, DOI: 10.1182/blood.2020005018.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD4-Positive T-LymphocytesCytokinesDisease Models, AnimalErythroblastosis, FetalErythrocyte TransfusionErythrocytesFemaleHumansImmunization, PassiveInterferon Type IIsoantigensKell Blood-Group SystemMembrane GlycoproteinsMetalloendopeptidasesMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicPhagocytosisPoly I-CPregnancyConceptsRed blood cellsSerum monocyte chemoattractant protein-1Monocyte chemoattractant protein-1Blood cellsHuman KEL glycoproteinPolyinosinic-polycytidilic acidTransfused red blood cellsType 1 IFNType I IFN receptorChemoattractant protein-1Type 1 interferonI IFN receptorMurine red blood cellsRecipient CD4Recipient inflammationIFN administrationSerum cytokinesInflammatory monocytesRecipient treatmentInterleukin-6Hemolytic diseaseT cellsMurine modelAlloimmunizationKnockout miceCoast-to-Coast Spread of SARS-CoV-2 during the Early Epidemic in the United States
Fauver JR, Petrone ME, Hodcroft EB, Shioda K, Ehrlich HY, Watts AG, Vogels CBF, Brito AF, Alpert T, Muyombwe A, Razeq J, Downing R, Cheemarla NR, Wyllie AL, Kalinich CC, Ott IM, Quick J, Loman NJ, Neugebauer KM, Greninger AL, Jerome KR, Roychoudhury P, Xie H, Shrestha L, Huang ML, Pitzer VE, Iwasaki A, Omer SB, Khan K, Bogoch II, Martinello RA, Foxman EF, Landry ML, Neher RA, Ko AI, Grubaugh ND. Coast-to-Coast Spread of SARS-CoV-2 during the Early Epidemic in the United States. Cell 2020, 181: 990-996.e5. PMID: 32386545, PMCID: PMC7204677, DOI: 10.1016/j.cell.2020.04.021.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Federal travel restrictionsSARS-CoV-2 transmissionCOVID-19 patientsCoronavirus SARS-CoV-2SARS-CoV-2 introductionsEarly SARS-CoV-2 transmissionPattern of spreadSustained transmissionLocal surveillanceEarly epidemicInternational importationCOVID-19 outbreakUnited StatesViral genomeInternational travel patternsPatientsCritical needTravel restrictions
2018
Regional Differences in Airway Epithelial Cells Reveal Tradeoff between Defense against Oxidative Stress and Defense against Rhinovirus
Mihaylova VT, Kong Y, Fedorova O, Sharma L, Dela Cruz CS, Pyle AM, Iwasaki A, Foxman EF. Regional Differences in Airway Epithelial Cells Reveal Tradeoff between Defense against Oxidative Stress and Defense against Rhinovirus. Cell Reports 2018, 24: 3000-3007.e3. PMID: 30208323, PMCID: PMC6190718, DOI: 10.1016/j.celrep.2018.08.033.Peer-Reviewed Original ResearchConceptsRIG-I stimulationAntiviral responseRhinovirus infectionBronchial airway epithelial cellsAcute respiratory infectionsEpithelial cellsRobust antiviral responseAirway epithelial cellsPrimary human nasalAirway damageRespiratory infectionsAirway microenvironmentAsthma attacksNasal mucosaLeading causeNrf2 knockdownNasal cellsNrf2 activationHuman nasalEpithelial defenseHost defenseBronchial cellsInfectionOxidative stressRhinovirus
2017
Antiviral Response in the Nasopharynx Identifies Patients With Respiratory Virus Infection
Landry ML, Foxman EF. Antiviral Response in the Nasopharynx Identifies Patients With Respiratory Virus Infection. The Journal Of Infectious Diseases 2017, 217: 897-905. PMID: 29281100, PMCID: PMC5853594, DOI: 10.1093/infdis/jix648.Peer-Reviewed Original ResearchConceptsRespiratory virusesNasopharyngeal swabsViral infectionCXCL10 protein levelsPatient nasopharyngeal swabsRespiratory virus infectionsHuman nasal epithelial cellsManagement of patientsRespiratory virus detectionNasal epithelial cellsSingle host proteinVirus detectionSimple diagnostic testIdentifies patientsRespiratory symptomsRespiratory infectionsRespiratory illnessHigh burdenVirus infectionReceptor RIGCost-effective testAntiviral responseAccurate diagnosisDiagnostic testsInfection
2016
Early local immune defences in the respiratory tract
Iwasaki A, Foxman EF, Molony RD. Early local immune defences in the respiratory tract. Nature Reviews Immunology 2016, 17: 7-20. PMID: 27890913, PMCID: PMC5480291, DOI: 10.1038/nri.2016.117.Peer-Reviewed Original ResearchConceptsRespiratory tractImmune responseDendritic cellsType 2 immune responsesType 1 immune responsePlasmacytoid dendritic cellsEpithelial cellsTissue-resident lymphocytesLower respiratory tractType of infectionUpper respiratory tractAirway epithelial cellsLocal immune defensePattern recognition receptorsAntimicrobial host defenseLymphoid cell typesCell typesRespiratory infectionsEffector cellsSecrete cytokinesAllergen resultsInnate sensorsMast cellsAirway cellsPathological inflammationTwo interferon-independent double-stranded RNA-induced host defense strategies suppress the common cold virus at warm temperature
Foxman EF, Storer JA, Vanaja K, Levchenko A, Iwasaki A. Two interferon-independent double-stranded RNA-induced host defense strategies suppress the common cold virus at warm temperature. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: 8496-8501. PMID: 27402752, PMCID: PMC4968739, DOI: 10.1073/pnas.1601942113.Peer-Reviewed Original ResearchConceptsIFN-independent mechanismsEpithelial cellsHost defense strategiesHost cell deathIFN inductionHuman bronchial epithelial cellsReduced virus productionCommon cold virusInfected epithelial cellsB-cell lymphoma 2 (Bcl-2) overexpressionBronchial epithelial cellsDiverse stimuliViral replicationAntiviral pathwaysCell deathH1-HeLa cellsTemperature-dependent replicationCell typesSingle replication cycleTemperature-dependent growthReplication cycleWarmer temperaturesCool temperaturesDefense strategiesType 1 IFN response
2011
Genome–virome interactions: examining the role of common viral infections in complex disease
Foxman EF, Iwasaki A. Genome–virome interactions: examining the role of common viral infections in complex disease. Nature Reviews Microbiology 2011, 9: 254-264. PMID: 21407242, PMCID: PMC3678363, DOI: 10.1038/nrmicro2541.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesAssociation studiesHuman genetic variationLarge regulatory networkHost-virus interactionsCrohn's diseaseRegulatory networksHost genesGenetic variationModel hostGenomic technologiesAutophagy pathwayAntiviral defenseViral infectionAdditional host factorsEnvironmental conditionsComplex diseasesCommon viral infectionsCases of asthmaSubsequent disease developmentGenesHostHost factorsDisease developmentParticular virus
2004
Use of the Fetal Fibronectin Test in Decisions to Admit to Hospital for Preterm Labor
Foxman EF, Jarolim P. Use of the Fetal Fibronectin Test in Decisions to Admit to Hospital for Preterm Labor. Clinical Chemistry 2004, 50: 663-665. PMID: 14981040, DOI: 10.1373/clinchem.2003.028720.Peer-Reviewed Original Research
1999
Integrating Conflicting Chemotactic Signals
Foxman E, Kunkel E, Butcher E. Integrating Conflicting Chemotactic Signals. Journal Of Cell Biology 1999, 147: 577-588. PMID: 10545501, PMCID: PMC2151176, DOI: 10.1083/jcb.147.3.577.Peer-Reviewed Original Research
1998
Chemotaxis Assays for Eukaryotic Cells
Zigmond S, Foxman E, Segall J. Chemotaxis Assays for Eukaryotic Cells. Current Protocols In Cell Biology 1998, 00: 12.1.1-12.1.29. PMID: 18228315, DOI: 10.1002/0471143030.cb1201s00.Peer-Reviewed Original Research