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, 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 microbesCells
2023
Pharmacological disruption of mSWI/SNF complex activity restricts SARS-CoV-2 infection
Wei J, Patil A, Collings C, Alfajaro M, Liang Y, Cai W, Strine M, Filler R, DeWeirdt P, Hanna R, Menasche B, Ökten A, Peña-Hernández M, Klein J, McNamara A, Rosales R, McGovern B, Luis Rodriguez M, García-Sastre A, White K, Qin Y, Doench J, Yan Q, Iwasaki A, Zwaka T, Qi J, Kadoch C, Wilen C. Pharmacological disruption of mSWI/SNF complex activity restricts SARS-CoV-2 infection. Nature Genetics 2023, 55: 471-483. PMID: 36894709, PMCID: PMC10011139, DOI: 10.1038/s41588-023-01307-z.Peer-Reviewed Original ResearchConceptsMSWI/SNF complexesAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionHost-directed therapeutic targetSyndrome coronavirus 2 infectionSARS-CoV-2 infectionSWItch/Sucrose Non-Fermentable (SWI/SNF) chromatinSARS-CoV-2 susceptibilityNon-fermentable (SWI/SNF) chromatinCoronavirus 2 infectionEnzyme 2 (ACE2) expressionSARS-CoV-2 variantsHuman cell typesPrimary human cell typesAirway epithelial cellsDrug-resistant variantsNew drug targetsChromatin accessibilitySNF complexACE2 locusACE2 expressionFactor complexHost determinantsTherapeutic targetConfer resistance
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 ResearchGenome-wide bidirectional CRISPR screens identify mucins as host factors modulating SARS-CoV-2 infection
Biering SB, Sarnik SA, Wang E, Zengel JR, Leist SR, Schäfer A, Sathyan V, Hawkins P, Okuda K, Tau C, Jangid AR, Duffy CV, Wei J, Gilmore RC, Alfajaro MM, Strine MS, Nguyenla X, Van Dis E, Catamura C, Yamashiro LH, Belk JA, Begeman A, Stark JC, Shon DJ, Fox DM, Ezzatpour S, Huang E, Olegario N, Rustagi A, Volmer AS, Livraghi-Butrico A, Wehri E, Behringer RR, Cheon DJ, Schaletzky J, Aguilar HC, Puschnik AS, Button B, Pinsky BA, Blish CA, Baric RS, O’Neal W, Bertozzi CR, Wilen CB, Boucher RC, Carette JE, Stanley SA, Harris E, Konermann S, Hsu PD. Genome-wide bidirectional CRISPR screens identify mucins as host factors modulating SARS-CoV-2 infection. Nature Genetics 2022, 54: 1078-1089. PMID: 35879412, PMCID: PMC9355872, DOI: 10.1038/s41588-022-01131-x.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionHost factorsSARS-CoV-2 entry factors ACE2SARS-CoV-2-host interactionsSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Diverse respiratory virusesMild respiratory illnessRespiratory distress syndromeSARS-CoV-2 host factorsHost-directed therapeuticsSyndrome coronavirus 2Coronavirus disease 2019Human lung epithelial cellsRange of symptomsHost defense mechanismsLung epithelial cellsGenome-wide CRISPR knockoutDistress syndromeRespiratory virusesRespiratory illnessCoronavirus 2Cell cycle regulationHigh molecular weight glycoproteinsHigh-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
Single-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 replicationDiscovery and functional interrogation of SARS-CoV-2 RNA-host protein interactions
Flynn RA, Belk JA, Qi Y, Yasumoto Y, Wei J, Alfajaro MM, Shi Q, Mumbach MR, Limaye A, DeWeirdt PC, Schmitz CO, Parker KR, Woo E, Chang HY, Horvath TL, Carette JE, Bertozzi CR, Wilen CB, Satpathy AT. Discovery and functional interrogation of SARS-CoV-2 RNA-host protein interactions. Cell 2021, 184: 2394-2411.e16. PMID: 33743211, PMCID: PMC7951565, DOI: 10.1016/j.cell.2021.03.012.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 RNASARS-CoV-2Virus-induced cell deathHost protein interactionsRNA-binding proteinActive infectionRNA virusesHost-virus interfaceGlobal mortalityTherapeutic benefitCRISPR screensAntiviral factorsProtein interactionsAntiviral activityViral specificityHost pathwaysFunctional RNA-binding proteinsFunctional connectionsRNA-centric approachesCell deathHost proteinsVirusFunctional interrogationRNAComprehensive catalogNeuroinvasion 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
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 antagonistsMouse 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
2019
Dual Recognition of Sialic Acid and αGal Epitopes by the VP8* Domains of the Bovine Rotavirus G6P[5] WC3 and of Its Mono-reassortant G4P[5] RotaTeq Vaccine Strains
Alfajaro M, Kim J, Barbé L, Cho E, Park J, Soliman M, Baek Y, Kang M, Kim S, Kim G, Park S, Le Pendu J, Cho K. Dual Recognition of Sialic Acid and αGal Epitopes by the VP8* Domains of the Bovine Rotavirus G6P[5] WC3 and of Its Mono-reassortant G4P[5] RotaTeq Vaccine Strains. Journal Of Virology 2019, 93: 10.1128/jvi.00941-19. PMID: 31243129, PMCID: PMC6714814, DOI: 10.1128/jvi.00941-19.Peer-Reviewed Original ResearchConceptsHisto-blood group antigensRotaTeq vaccineIntestinal epithelial cellsAlternative receptorSialic acidVaccine strainGroup antigensSevere rotavirus diseaseEpithelial cellsHuman intestinal epithelial cellsHuman small intestinal epithelial cellsNatural human infectionBearing strainsSmall intestinal epithelial cellsRotaTeq vaccine strainsMA-104 cellsTight junction proteinsGroup A rotavirusesRotavirus diseaseSevere diarrheaIntestinal enteroidsGroup ASurface sialic acidΑGal epitopesImportant cause
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 studyCellsPorcine sapovirus Cowden strain enters LLC-PK cells via clathrin- and cholesterol-dependent endocytosis with the requirement of dynamin II
Soliman M, Kim D, Kim C, Seo J, Kim J, Park J, Alfajaro M, Baek Y, Cho E, Park S, Kang M, Chang K, Goodfellow I, Cho K. Porcine sapovirus Cowden strain enters LLC-PK cells via clathrin- and cholesterol-dependent endocytosis with the requirement of dynamin II. Veterinary Research 2018, 49: 92. PMID: 30223898, PMCID: PMC6142377, DOI: 10.1186/s13567-018-0584-0.Peer-Reviewed Original ResearchConceptsDynamin IIActin rearrangementLate endosomesDN mutantsLLC-PK cellsDynamin GTPase activityClathrin-mediated endocytosisCowden strainClathrin-mediated internalizationDominant negative mutantCholesterol-dependent endocytosisInhibition of caveolaeVesicle internalizationCholesterol-sequestering drugEndosomal traffickingEarly endosomesSiRNA depletionNegative mutantGTPase activityClathrinEndocytosisEndosomal acidificationMutantsEndosomesCell entryBovine Nebovirus Interacts with a Wide Spectrum of Histo-Blood Group Antigens
Cho E, Soliman M, Alfajaro M, Kim J, Seo J, Park J, Kim D, Baek Y, Kang M, Park S, Le Pendu J, Cho K. Bovine Nebovirus Interacts with a Wide Spectrum of Histo-Blood Group Antigens. Journal Of Virology 2018, 92: 10.1128/jvi.02160-17. PMID: 29467317, PMCID: PMC5899197, DOI: 10.1128/jvi.02160-17.Peer-Reviewed Original ResearchConceptsFucose epitopesTerminal sialic acidHost speciesVirus-like particlesHisto-blood group antigensCell surface carbohydrate moietiesMammalian host speciesEnteric calicivirusesAttachment factorsSialic acidCultured cell linesBovine digestive tractSurface carbohydrate moietiesCell carbohydratesHost rangeType speciesViral generaHBGA recognitionCarbohydrate moietyBiochemical assaysSpecific enzymesCellular receptorsSynthetic histo-blood group antigensReplication cycleSpeciesActivation 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
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 Research
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
2015
Genetic diversity of the VP7, VP4 and VP6 genes of Korean porcine group C rotaviruses
Jeong Y, Matthijnssens J, Kim D, Kim J, Alfajaro M, Park J, Hosmillo M, Son K, Soliman M, Baek Y, Kwon J, Choi J, Kang M, Cho K. Genetic diversity of the VP7, VP4 and VP6 genes of Korean porcine group C rotaviruses. Veterinary Microbiology 2015, 176: 61-69. PMID: 25592760, DOI: 10.1016/j.vetmic.2014.12.024.Peer-Reviewed Original ResearchConceptsGenetic diversityPorcine group C rotavirusPorcine RVCRVC strainsLarge genetic diversityVP6 geneGroup C rotavirusFrequent reassortment eventsStrong geographical differencesPhylogenetic dataPhylogenetic analysisHost speciesHuman RVCORF sequencesC rotavirusReassortment eventsGene segmentsPig industryG7 genotypeImportant pathogenGenesDiversityEconomic impactVP4 sequencesDefinitive cut
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
2011
Reassortment among bovine, porcine and human rotavirus strains results in G8P[7] and G6P[7] strains isolated from cattle in South Korea
Park S, Matthijnssens J, Saif L, Kim H, Park J, Alfajaro M, Kim D, Son K, Yang D, Hyun B, Kang M, Cho K. Reassortment among bovine, porcine and human rotavirus strains results in G8P[7] and G6P[7] strains isolated from cattle in South Korea. Veterinary Microbiology 2011, 152: 55-66. PMID: 21592683, DOI: 10.1016/j.vetmic.2011.04.015.Peer-Reviewed Original ResearchConceptsGenotype constellationT1-E1-H1 genotypesH1 genotype constellationFull-length ORFDetailed phylogenetic analysisGroup A rotavirusesC1-M2Phylogenetic analysisComplete genomeN2-T6Genome constellationM2-A3VP1-4I5-R1Bovine group A rotavirusesHeterologous speciesI2-R2A1-N1ReassortmentG8 genotypeSingle strainReassortant strainsGenotypesStrainsGenome