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-oldVirusConsiderations for viral co-infection studies in human populations
Chin T, Foxman E, Watkins T, Lipsitch M. Considerations for viral co-infection studies in human populations. MBio 2024, 15: e00658-24. PMID: 38847531, PMCID: PMC11253623, DOI: 10.1128/mbio.00658-24.Peer-Reviewed Original Research
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 ResearchCausal identification of single-cell experimental perturbation effects with CINEMA-OT
Dong M, Wang B, Wei J, de O. Fonseca A, Perry C, Frey A, Ouerghi F, Foxman E, Ishizuka J, Dhodapkar R, van Dijk D. Causal identification of single-cell experimental perturbation effects with CINEMA-OT. Nature Methods 2023, 20: 1769-1779. PMID: 37919419, PMCID: PMC10630139, DOI: 10.1038/s41592-023-02040-5.Peer-Reviewed Original ResearchViral Interference During Influenza A–SARS-CoV-2 Coinfection of the Human Airway Epithelium and Reversal by Oseltamivir
Cheemarla N, Watkins T, Mihaylova V, Foxman E. Viral Interference During Influenza A–SARS-CoV-2 Coinfection of the Human Airway Epithelium and Reversal by Oseltamivir. The Journal Of Infectious Diseases 2023, 229: 1430-1434. PMID: 37722683, PMCID: PMC11095529, DOI: 10.1093/infdis/jiad402.Peer-Reviewed Original ResearchSARS-CoV-2 replicationSARS-CoV-2IAV replicationHuman airway epithelial culturesHuman airway epitheliumAirway epithelial culturesHost antiviral responseRobust interferon responseInfluenza infectionRespiratory virusesAirway epitheliumViral infectionAntiviral responseViral interferenceCoinfecting virusSimultaneous infectionHost cell defenseInterferon responseCoinfectionInfectionEpithelial culturesOseltamivirInfluenzaVirusCell defensePLSCR1 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
Complement Plays a Critical Role in Inflammation-Induced Immunoprophylaxis Failure in Mice
Escamilla-Rivera V, Santhanakrishnan M, Liu J, Gibb DR, Forsmo JE, Foxman EF, Eisenbarth SC, Luckey CJ, Zimring JC, Hudson KE, Stowell SR, Hendrickson JE. Complement Plays a Critical Role in Inflammation-Induced Immunoprophylaxis Failure in Mice. Frontiers In Immunology 2021, 12: 704072. PMID: 34249009, PMCID: PMC8270673, DOI: 10.3389/fimmu.2021.704072.Peer-Reviewed Original ResearchConceptsImmunoprophylaxis failureRed blood cellsRBC transfusionComplement receptorsHuman KEL glycoproteinB cell activation thresholdWild-type micePresence of complementMurine red blood cellsTwo-hit modelRecipient inflammationIgG alloantibodiesInflammatory monocytesAdaptive immunityType miceB cellsRecipient complementTranslational relevanceKey cellsTransfusionMiceBlood cellsImmunoprophylaxis efficacyBaseline stateActivation thresholdDynamic 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 Research
2020
An in vivo atlas of host–pathogen transcriptomes during Streptococcus pneumoniae colonization and disease
D’Mello A, Riegler AN, Martínez E, Beno SM, Ricketts TD, Foxman EF, Orihuela CJ, Tettelin H. An in vivo atlas of host–pathogen transcriptomes during Streptococcus pneumoniae colonization and disease. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 33507-33518. PMID: 33318198, PMCID: PMC7777036, DOI: 10.1073/pnas.2010428117.Peer-Reviewed Original ResearchConceptsStreptococcus pneumoniae colonizationHost gene expression profilesHost defense pathwaysOrgan damagePneumoniae colonizationProinflammatory responseInvasive diseaseAnatomical sitesTherapeutic targetInterferon responseDisease statesDiseaseGene expression profilesLungOrgan-specific mannerVivoPneumoniaPathogenesisKidneyBloodResponseInterference 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 sensitivityExperimental Evolution of Human Rhinovirus Strains Adapting to Mouse Cells
Wasik B, Wasik B, Foxman E, Iwasaki A, Turner P. Experimental Evolution of Human Rhinovirus Strains Adapting to Mouse Cells. Genetic And Evolutionary Computation 2020, 145-157. DOI: 10.1007/978-3-030-39831-6_12.Peer-Reviewed Original ResearchMouse cellsIdentical selection pressuresExperimental evolution studiesLaboratory tissue cultureCommon cold illnessesViral capsid geneMolecular divergenceExperimental evolutionReplication genesSelection pressureRelated populationsGenetic changesRNA virusesHuman rhinovirus strainsCapsid geneEvolution studiesRV-1BInnate immunityGenesTissue cultureDifferent strainsCellsLA-4 cellsHostMouse hostPoly(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