2020
Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling
Israelow B, Song E, Mao T, Lu P, Meir A, Liu F, Alfajaro MM, Wei J, Dong H, Homer RJ, Ring A, Wilen CB, Iwasaki A. Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling. Journal Of Experimental Medicine 2020, 217: e20201241. PMID: 32750141, PMCID: PMC7401025, DOI: 10.1084/jem.20201241.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin-Converting Enzyme 2AnimalsBetacoronavirusCell Line, TumorCoronavirus InfectionsCOVID-19DependovirusDisease Models, AnimalFemaleHumansInflammationInterferon Type ILungMaleMiceMice, Inbred C57BLMice, TransgenicPandemicsParvoviridae InfectionsPeptidyl-Dipeptidase APneumonia, ViralSARS-CoV-2Signal TransductionVirus ReplicationConceptsSARS-CoV-2Type I interferonMouse modelI interferonRobust SARS-CoV-2 infectionSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2SARS-CoV-2 infectionRespiratory syndrome coronavirus 2SARS-CoV-2 replicationCOVID-19 patientsSyndrome coronavirus 2Patient-derived virusesSignificant fatality ratePathological findingsInflammatory rolePathological responseEnzyme 2Receptor angiotensinFatality rateVaccine developmentGenetic backgroundViral replicationCoronavirus diseaseMice
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 SapovirusInfectionActivation of PI3K, Akt, and ERK during early rotavirus infection leads to V-ATPase-dependent endosomal acidification required for uncoating
Soliman M, Seo J, Kim D, Kim J, Park J, Alfajaro M, Baek Y, Cho E, Kwon J, Choi J, Kang M, Park S, Cho K. Activation of PI3K, Akt, and ERK during early rotavirus infection leads to V-ATPase-dependent endosomal acidification required for uncoating. PLOS Pathogens 2018, 14: e1006820. PMID: 29352319, PMCID: PMC5792019, DOI: 10.1371/journal.ppat.1006820.Peer-Reviewed Original ResearchMeSH KeywordsAcidsAnimalsCaco-2 CellsCapsid ProteinsCattleCells, CulturedEndosomesEnzyme ActivationExtracellular Signal-Regulated MAP KinasesHaplorhiniHumansHydrogen-Ion ConcentrationPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktRotavirusRotavirus InfectionsSf9 CellsSignal TransductionVacuolar Proton-Translocating ATPasesVirus UncoatingConceptsMEK/ERK pathwayV-ATPasePI3K/AktSubunit EOuter capsid proteinEndosomal acidificationLate endosomesERK pathwayCapsid proteinPI3KEarly infection eventsMEK/ERKCell surface receptorsImmunoprecipitation assaysPPI3KVirus traffickingProximity ligationMultistep bindingSurface receptorsAktViral progenyViral uncoatingERKRVA strainsEndosomes
2017
Activation of COX-2/PGE2 Promotes Sapovirus Replication via the Inhibition of Nitric Oxide Production
Alfajaro M, Choi J, Kim D, Seo J, Kim J, Park J, Soliman M, Baek Y, Cho E, Kwon J, Kwon H, Park S, Lee W, Kang M, Hosmillo M, Goodfellow I, Cho K. Activation of COX-2/PGE2 Promotes Sapovirus Replication via the Inhibition of Nitric Oxide Production. Journal Of Virology 2017, 91: 10.1128/jvi.01656-16. PMID: 27881647, PMCID: PMC5244346, DOI: 10.1128/jvi.01656-16.Peer-Reviewed Original ResearchConceptsCOX/PGENonsteroidal anti-inflammatory drugsAnti-inflammatory drugsCOX-2Sapovirus infectionAcute gastroenteritisProstaglandin ECOX-1/2 inhibitor indomethacinAntiviral effector mechanismsCOX-2 specific inhibitor NS-398Severe acute gastroenteritisCOX-1 levelsInhibitor NS-398New targetsNitric oxide synthaseProduction of PGENitric oxide productionCOX-2 mRNASmall interfering RNAsPorcine sapovirusMajor etiological agentPotential new targetsInhibitor indomethacinOxide synthaseEffector mechanisms