2020
Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection
Wei J, Alfajaro MM, DeWeirdt PC, Hanna RE, Lu-Culligan WJ, Cai WL, Strine MS, Zhang SM, Graziano VR, Schmitz CO, Chen JS, Mankowski MC, Filler RB, Ravindra NG, Gasque V, de Miguel FJ, Patil A, Chen H, Oguntuyo KY, Abriola L, Surovtseva YV, Orchard RC, Lee B, Lindenbach BD, Politi K, van Dijk D, Kadoch C, Simon MD, Yan Q, Doench JG, Wilen CB. Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection. Cell 2020, 184: 76-91.e13. PMID: 33147444, PMCID: PMC7574718, DOI: 10.1016/j.cell.2020.10.028.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin-Converting Enzyme 2AnimalsCell LineChlorocebus aethiopsClustered Regularly Interspaced Short Palindromic RepeatsCoronavirusCoronavirus InfectionsCOVID-19Gene Knockout TechniquesGene Regulatory NetworksGenome-Wide Association StudyHEK293 CellsHMGB1 ProteinHost-Pathogen InteractionsHumansSARS-CoV-2Vero CellsVirus InternalizationConceptsSARS-CoV-2 infectionSARS-CoV-2Vesicular stomatitis virusGenome-wide CRISPR screenSWI/SNF chromatinSARS-CoV-2 host factorsAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionTherapeutic targetHost factorsCoronavirus disease 2019 (COVID-19) pathogenesisSyndrome coronavirus 2 infectionCRISPR screensHost genesGene productsMiddle East respiratory syndrome CoVCoronavirus 2 infectionGenetic hitsHuman cellsSARS-CoV-2 spikeNovel therapeutic targetPotential therapeutic targetVero E6 cellsSARS-CoV-1Small molecule antagonists
2018
Phosphatidylinositol 3-Kinase/Akt and MEK/ERK Signaling Pathways Facilitate Sapovirus Trafficking and Late Endosomal Acidification for Viral Uncoating in LLC-PK Cells
Soliman M, Kim D, Park J, Kim J, Alfajaro M, Baek Y, Cho E, Park C, Kang M, Park S, Cho K. Phosphatidylinositol 3-Kinase/Akt and MEK/ERK Signaling Pathways Facilitate Sapovirus Trafficking and Late Endosomal Acidification for Viral Uncoating in LLC-PK Cells. Journal Of Virology 2018, 92: 10.1128/jvi.01674-18. PMID: 30282712, PMCID: PMC6258943, DOI: 10.1128/jvi.01674-18.Peer-Reviewed Original ResearchConceptsMEK/ERKCell surface carbohydrate receptorsLate endosomesPI3K/AktSmall interfering RNAsEndosomal acidificationPI3KEarly endosomesExtracellular signal-regulated kinaseViral uncoatingSignal-regulated kinaseV-ATPase proton pumpCell surface receptorsHost cell entryEarly activationEntry processERK moleculesInterfering RNAsEndosomesCarbohydrate receptorsUse of inhibitorsProton pumpERKSurface receptorsAktRotavirus-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 studyCells
2017
Glycan-specificity of four neuraminidase-sensitive animal rotavirus strains
Kim J, Kim D, Seo J, Park J, Alfajaro M, Soliman M, Baek Y, Cho E, Kwon H, Park S, Kang M, Cho K. Glycan-specificity of four neuraminidase-sensitive animal rotavirus strains. Veterinary Microbiology 2017, 207: 159-163. PMID: 28757018, DOI: 10.1016/j.vetmic.2017.06.016.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineFibroblastsHumansMembrane GlycoproteinsNeuraminidaseRotavirusVirus AttachmentActivation 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
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
Both 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 acts
2012
Anti-rotaviral effects of Glycyrrhiza uralensis extract in piglets with rotavirus diarrhea
Alfajaro M, Kim H, Park J, Ryu E, Kim J, Jeong Y, Kim D, Hosmillo M, Son K, Lee J, Kwon H, Ryu Y, Park S, Park S, Lee W, Cho K. Anti-rotaviral effects of Glycyrrhiza uralensis extract in piglets with rotavirus diarrhea. Virology Journal 2012, 9: 310. PMID: 23244491, PMCID: PMC3547719, DOI: 10.1186/1743-422x-9-310.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornAnti-Inflammatory Agents, Non-SteroidalAntiviral AgentsCell LineColostrumDiarrheaDose-Response Relationship, DrugDrug Evaluation, PreclinicalFecesGlycyrrhiza uralensisInterleukin-8Intestine, SmallMAP Kinase Signaling SystemModels, AnimalNF-kappa BPhytotherapyPlant ExtractsPlant RootsRNA, MessengerRotavirusRotavirus InfectionsSpleenSwineSwine DiseasesTumor Necrosis Factor-alphaVirus SheddingConceptsInflammation-related cytokinesGlycyrrhiza uralensis extractMRNA expression levelsSmall intestineRotavirus diarrheaRotaviral enteritisAnti-rotaviral effectAnti-inflammatory effectsFecal virus sheddingOnset of diarrheaColostrum-deprived pigletsExpression levelsIntestinal lesion scoresFecal consistency scoreAntiviral efficacyVirus sheddingHistological changesSevere gastroenteritisFecal virusAntiviral agentsDiarrheaLesion scoresViable medicationsHerbal medicineAntiviral properties