2024
Intestinal tuft cell immune privilege enables norovirus persistence
Strine M, Fagerberg E, Darcy P, Barrón G, Filler R, Alfajaro M, D'Angelo-Gavrish N, Wang F, Graziano V, Menasché B, Damo M, Wang Y, Howitt M, Lee S, Joshi N, Mucida D, Wilen C. Intestinal tuft cell immune privilege enables norovirus persistence. Science Immunology 2024, 9: eadi7038. PMID: 38517952, PMCID: PMC11555782, DOI: 10.1126/sciimmunol.adi7038.Peer-Reviewed Original ResearchConceptsCD8<sup>+</sup> T cellsIntestinal tuft cellsT cellsTufted cellsViral persistenceSite of viral persistenceChemosensory epithelial cellsNormal antigen presentationImmune-privileged nicheIntestinal stem cellsMemory phenotypeImmune privilegeImmune escapeReporter miceAntigen presentationChronic infectionCytotoxic capacityEpithelial cellsNorovirus infectionStem cellsCell interactionsInfectionCell survivalEnteric microbesCellsHuman iPSC-Based Model of COPD to Investigate Disease Mechanisms, Predict SARS-COV-2 Outcome, and Test Preventive Immunotherapy
Dagher R, Moldobaeva A, Gubbins E, Clark S, Alfajaro M, Wilen C, Hawkins F, Qu X, Chiang C, Li Y, Clarke L, Ikeda Y, Brown C, Kolbeck R, Ma Q, Rojas M, Koff J, Ghaedi M. Human iPSC-Based Model of COPD to Investigate Disease Mechanisms, Predict SARS-COV-2 Outcome, and Test Preventive Immunotherapy. Stem Cells 2024, 42: 230-250. PMID: 38183264, DOI: 10.1093/stmcls/sxad094.Peer-Reviewed Original ResearchSARS-CoV-2 infectionAlveolar nicheSARS-CoV-2 outcomesAberrant inflammatory responseModels of COPDDisease-specific mechanismsInflammation/Preventive immunotherapyChronic inflammationEpithelial damageInflammatory responseLung tissueCOPDNovel therapeuticsEpithelial-mesenchymal interactionsMitochondrial dysfunctionInfectionDisease mechanismsHuman iPSCCell deathFibroblast modelSingle-cell levelRepair mechanismsIPSCsImmunotherapy
2022
Tuft-cell-intrinsic and -extrinsic mediators of norovirus tropism regulate viral immunity
Strine M, Alfajaro M, Graziano V, Song J, Hsieh L, Hill R, Guo J, VanDussen K, Orchard R, Baldridge M, Lee S, Wilen C. Tuft-cell-intrinsic and -extrinsic mediators of norovirus tropism regulate viral immunity. Cell Reports 2022, 41: 111593. PMID: 36351394, PMCID: PMC9662704, DOI: 10.1016/j.celrep.2022.111593.Peer-Reviewed Original ResearchHigh-affinity, neutralizing antibodies to SARS-CoV-2 can be made without T follicular helper cells
Chen JS, Chow RD, Song E, Mao T, Israelow B, Kamath K, Bozekowski J, Haynes WA, Filler RB, Menasche BL, Wei J, Alfajaro MM, Song W, Peng L, Carter L, Weinstein JS, Gowthaman U, Chen S, Craft J, Shon JC, Iwasaki A, Wilen CB, Eisenbarth SC. High-affinity, neutralizing antibodies to SARS-CoV-2 can be made without T follicular helper cells. Science Immunology 2022, 7: eabl5652. PMID: 34914544, PMCID: PMC8977051, DOI: 10.1126/sciimmunol.abl5652.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionSARS-CoV-2Follicular helper cellsB cell responsesHelper cellsAntibody productionCell responsesSARS-CoV-2 vaccinationB-cell receptor sequencingSevere COVID-19Cell receptor sequencingIndependent antibodiesT cell-B cell interactionsViral inflammationAntiviral antibodiesImmunoglobulin class switchingVirus infectionGerminal centersViral infectionClonal repertoireInfectionAntibodiesClass switchingCOVID-19Patients
2021
Neuroinvasion of SARS-CoV-2 in human and mouse brain
Song E, Zhang C, Israelow B, Lu-Culligan A, Prado AV, Skriabine S, Lu P, Weizman OE, Liu F, Dai Y, Szigeti-Buck K, Yasumoto Y, Wang G, Castaldi C, Heltke J, Ng E, Wheeler J, Alfajaro MM, Levavasseur E, Fontes B, Ravindra NG, Van Dijk D, Mane S, Gunel M, Ring A, Kazmi SAJ, Zhang K, Wilen CB, Horvath TL, Plu I, Haik S, Thomas JL, Louvi A, Farhadian SF, Huttner A, Seilhean D, Renier N, Bilguvar K, Iwasaki A. Neuroinvasion of SARS-CoV-2 in human and mouse brain. Journal Of Experimental Medicine 2021, 218: e20202135. PMID: 33433624, PMCID: PMC7808299, DOI: 10.1084/jem.20202135.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Central nervous systemSARS-CoV-2 neuroinvasionImmune cell infiltratesCOVID-19 patientsType I interferon responseMultiple organ systemsCOVID-19I interferon responseHuman brain organoidsNeuroinvasive capacityCNS infectionsCell infiltrateNeuronal infectionPathological featuresCortical neuronsRespiratory diseaseDirect infectionCerebrospinal fluidNervous systemMouse brainInterferon responseOrgan systemsHuman ACE2Infection
2019
Early Porcine Sapovirus Infection Disrupts Tight Junctions and Uses Occludin as a Coreceptor
Alfajaro M, Cho E, Kim D, Kim J, Park J, Soliman M, Baek Y, Park C, Kang M, Park S, Cho K. Early Porcine Sapovirus Infection Disrupts Tight Junctions and Uses Occludin as a Coreceptor. Journal Of Virology 2019, 93: 10.1128/jvi.01773-18. PMID: 30463963, PMCID: PMC6364031, DOI: 10.1128/jvi.01773-18.Peer-Reviewed Original ResearchConceptsSevere acute gastroenteritisClaudin-1Acute gastroenteritisEntry factorsTight junctionsTJ proteinsLLC-PK cellsAdhesion molecule-1Common causative agentChinese hamster ovaryDisrupts tight junctionsIntestinal epithelial cellsTransepithelial electrical resistanceHisto-blood groupTJ protein occludinRole of TJsMolecule-1Functional coreceptorInfectionTerminal sialic acidAffordable drugsProtein occludinOccludinSpecific antibodiesEpithelial cells
2018
Rotavirus-Induced Early Activation of the RhoA/ROCK/MLC Signaling Pathway Mediates the Disruption of Tight Junctions in Polarized MDCK Cells
Soliman M, Cho E, Park J, Kim J, Alfajaro M, Baek Y, Kim D, Kang M, Park S, Cho K. Rotavirus-Induced Early Activation of the RhoA/ROCK/MLC Signaling Pathway Mediates the Disruption of Tight Junctions in Polarized MDCK Cells. Scientific Reports 2018, 8: 13931. PMID: 30224682, PMCID: PMC6141481, DOI: 10.1038/s41598-018-32352-y.Peer-Reviewed Original ResearchConceptsTJ protein distributionTJ integrityTJ proteinsTight junctionsIntestinal epithelial tight junctionsEarly disruptionMDCK cellsEpithelial tight junctionsPrecise molecular mechanismsBovine NCDVRotavirus strainsEarly activationParacellular permeabilityCellular receptorsPerijunctional actomyosin ringTransepithelial resistanceEntry portalReversible decreaseSignaling pathwaysInfectionCoreceptorHarmful factorsMolecular mechanismsPresent studyCellsFeline calicivirus- and murine norovirus-induced COX-2/PGE2 signaling pathway has proviral effects
Alfajaro M, Cho E, Park J, Kim J, Soliman M, Baek Y, Kang M, Park S, Cho K. Feline calicivirus- and murine norovirus-induced COX-2/PGE2 signaling pathway has proviral effects. PLOS ONE 2018, 13: e0200726. PMID: 30021004, PMCID: PMC6051663, DOI: 10.1371/journal.pone.0200726.Peer-Reviewed Original ResearchConceptsCOX-2/COX-1/Production of PGE2COX-2 enzymePharmacological inhibitorsProviral effectCOX-1COX-2/PGE2Potential therapeutic candidateAddition of PGE2Small interfering RNAsSame virus familyReplication of virusesInfection of cellsTime-dependent mannerAntiviral effectMNV infectionTherapeutic candidatePGE2Virus replicationMNV replicationPathophysiological conditionsInhibitory effectGenus SapovirusInfection
2016
Porcine Sapelovirus Uses α2,3-Linked Sialic Acid on GD1a Ganglioside as a Receptor
Kim D, Son K, Koo K, Kim J, Alfajaro M, Park J, Hosmillo M, Soliman M, Baek Y, Cho E, Lee J, Kang M, Goodfellow I, Cho K. Porcine Sapelovirus Uses α2,3-Linked Sialic Acid on GD1a Ganglioside as a Receptor. Journal Of Virology 2016, 90: 4067-4077. PMID: 26865725, PMCID: PMC4810533, DOI: 10.1128/jvi.02449-15.Peer-Reviewed Original ResearchConceptsHisto-blood group antigensPorcine sapelovirusReproductive disordersSialic acidGroup antigensTerminal sialic acidSynthetic histo-blood group antigensEfficient drugsGlucosylceramide synthase inhibitorSynthase inhibitorLinkage-specific sialidasesInfectionGD1a gangliosidesReceptorsCell surface glycolipidsPneumoniaPolioencephalomyelitisTherapyCell surface carbohydratesAntigenGD1aHost cellsDisordersDrugsSapelovirus
2014
The prevalence of duck hepatitis A virus types 1 and 3 on Korean duck farms
Soliman M, Alfajaro M, Lee M, Jeong Y, Kim D, Son K, Kwon J, Choi J, Lim J, Choi J, Lee T, Cho K, Kang M. The prevalence of duck hepatitis A virus types 1 and 3 on Korean duck farms. Archives Of Virology 2014, 160: 493-498. PMID: 25359107, DOI: 10.1007/s00705-014-2264-3.Peer-Reviewed Original ResearchBoth α2,3- and α2,6-Linked Sialic Acids on O-Linked Glycoproteins Act as Functional Receptors for Porcine Sapovirus
Kim D, Hosmillo M, Alfajaro M, Kim J, Park J, Son K, Ryu E, Sorgeloos F, Kwon H, Park S, Lee W, Cho D, Kwon J, Choi J, Kang M, Goodfellow I, Cho K. Both α2,3- and α2,6-Linked Sialic Acids on O-Linked Glycoproteins Act as Functional Receptors for Porcine Sapovirus. PLOS Pathogens 2014, 10: e1004172. PMID: 24901849, PMCID: PMC4047124, DOI: 10.1371/journal.ppat.1004172.Peer-Reviewed Original ResearchConceptsHisto-blood group antigensFunctional receptorsSambucus nigra lectinSialic acidGroup antigensTreatment of cellsSynthetic histo-blood group antigensViral attachmentVirus bindingMaackia amurensis lectinPorcine sapovirusVibrio cholerae neuraminidaseRed blood cellsIntestinal tissue sectionsAcute gastroenteritisImportant causeInfectionBlood cellsVirus attachmentReceptorsPSAVSapovirusCellular receptorsTissue sectionsGlycoprotein actsEvidences and consequences of extra-intestinal spread of rotaviruses in humans and animals
Alfajaro M, Cho K. Evidences and consequences of extra-intestinal spread of rotaviruses in humans and animals. VirusDisease 2014, 25: 186-194. PMID: 25674584, PMCID: PMC4188184, DOI: 10.1007/s13337-014-0197-9.Peer-Reviewed Original Research
2013
Molecular epidemiology of Korean porcine sapeloviruses
Son K, Kim D, Matthijnssens J, Kwon H, Park J, Hosmillo M, Alfajaro M, Ryu E, Kim J, Kang M, Cho K. Molecular epidemiology of Korean porcine sapeloviruses. Archives Of Virology 2013, 159: 1175-1180. PMID: 24232913, PMCID: PMC7087272, DOI: 10.1007/s00705-013-1901-6.Peer-Reviewed Original ResearchConceptsGenetic diversityPorcine sapelovirusPronounced genetic diversityVP1 geneDiarrhea fecal samplesPhylogenetic analysisPrimer pairsPSV infectionGenesPCR assaysDiversityRT-PCRKorean pigsSapelovirusFecal samplesMolecular epidemiologyDiarrhea samplesBacteriaInfectionEnteric virusesHigher proportionAssaysPigsStrains
2010
Molecular detection of genotype 3 porcine hepatitis E virus in aborted fetuses and their sows
Hosmillo M, Jeong Y, Kim H, Park J, Nayak M, Alfajaro M, Collantes T, Park S, Ikuta K, Yunoki M, Kang M, Park S, Cho K. Molecular detection of genotype 3 porcine hepatitis E virus in aborted fetuses and their sows. Archives Of Virology 2010, 155: 1157-1161. PMID: 20458510, DOI: 10.1007/s00705-010-0679-z.Peer-Reviewed Original ResearchConceptsPorcine circovirus type 2Polymerase chain reactionHepatitis E virus RNAGenotype 3 HEVHEV-positive samplesHepatitis E virusReal-time RT-PCRViral copies/HEV infectionHEV RNATransplacental infectionCircovirus type 2E virusCopies/Type 2PCV2 coinfectionSerum samplesFetusesRT-PCRVirus RNAChain reactionReproductive failureInfectionReverse transcriptionMolecular detection