2023
DYRK1A promotes viral entry of highly pathogenic human coronaviruses in a kinase-independent manner
Strine M, Cai W, Wei J, Alfajaro M, Filler R, Biering S, Sarnik S, Chow R, Patil A, Cervantes K, Collings C, DeWeirdt P, Hanna R, Schofield K, Hulme C, Konermann S, Doench J, Hsu P, Kadoch C, Yan Q, Wilen C. DYRK1A promotes viral entry of highly pathogenic human coronaviruses in a kinase-independent manner. PLOS Biology 2023, 21: e3002097. PMID: 37310920, PMCID: PMC10263356, DOI: 10.1371/journal.pbio.3002097.Peer-Reviewed Original ResearchConceptsGenome-wide CRISPR/Cas9 screenCRISPR/Cas9 screenPathogenic human coronavirusesKinase-independent mannerRegulated kinase 1AProviral host factorNovel drug targetsMultiple cell typesDNA accessibilityHost factorsKinase functionHuman coronavirusesHost genesDistal enhancerNovel regulatorCas9 screenKinase 1AGene expressionNeuronal developmentDYRK1ADrug targetsDiverse coronavirusesProviral activityCell typesSevere acute respiratory syndrome coronavirus 2
2022
Genome-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 glycoproteins
2020
Cytidine Monophosphate N-Acetylneuraminic Acid Synthetase and Solute Carrier Family 35 Member A1 Are Required for Reovirus Binding and Infection
Urbanek K, Sutherland DM, Orchard RC, Wilen CB, Knowlton JJ, Aravamudhan P, Taylor GM, Virgin HW, Dermody TS. Cytidine Monophosphate N-Acetylneuraminic Acid Synthetase and Solute Carrier Family 35 Member A1 Are Required for Reovirus Binding and Infection. Journal Of Virology 2020, 95: 10.1128/jvi.01571-20. PMID: 33087464, PMCID: PMC7944449, DOI: 10.1128/jvi.01571-20.Peer-Reviewed Original ResearchConceptsSialic acid expressionMicroglial cellsCell surface expressionReovirus-induced cell deathReovirus infectionSialic acidMurine microglial BV2 cellsReovirus-induced diseaseMember A1Microglial BV2 cellsSurface expressionMurine microglial cellsCell deathReovirus bindingBV2 cellsViral tropismInfectionHost genesLow-level bindingCell surface receptorsHost factorsCell surfaceReceptorsSialic acid synthesisSurface receptorsGenome-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
2019
Noroviruses subvert the core stress granule component G3BP1 to promote viral VPg-dependent translation
Hosmillo M, Lu J, McAllaster MR, Eaglesham JB, Wang X, Emmott E, Domingues P, Chaudhry Y, Fitzmaurice TJ, Tung MK, Panas MD, McInerney G, Locker N, Wilen CB, Goodfellow IG. Noroviruses subvert the core stress granule component G3BP1 to promote viral VPg-dependent translation. ELife 2019, 8: e46681. PMID: 31403400, PMCID: PMC6739877, DOI: 10.7554/elife.46681.Peer-Reviewed Original ResearchConceptsViral positive-sense RNAFirst host factorHost factorsPositive-sense RNAPro-viral activityPositive-sense RNA virusesSense RNA virusesG3BP1 functionsRibosome recruitmentTranslation complexesTranslation initiationCRISPR screensProteomic analysisMurine norovirus infectionReplication complexSense RNANovel functionViral translationRNA virusesG3BP1Data uncoversNorovirus replicationLife cycleVPgGenus
2016
Discovery of a proteinaceous cellular receptor for a norovirus
Orchard RC, Wilen CB, Doench JG, Baldridge MT, McCune BT, Lee YC, Lee S, Pruett-Miller SM, Nelson CA, Fremont DH, Virgin HW. Discovery of a proteinaceous cellular receptor for a norovirus. Science 2016, 353: 933-936. PMID: 27540007, PMCID: PMC5484048, DOI: 10.1126/science.aaf1220.Peer-Reviewed Original ResearchConceptsProteinaceous receptorsMNoV infectionCellular machineryNoV replicationHuman cellsCell deathSpecies barrierCD300lfSpecies tropismPrimary cellsCellular receptorsCell linesMurine NoVHost factorsReplicationCause of gastroenteritisPrimary determinantNoV infectionReceptorsCellsEctodomainMachineryInfectionCrystal structureResidues
2014
The Major Cellular Sterol Regulatory Pathway Is Required for Andes Virus Infection
Petersen J, Drake MJ, Bruce EA, Riblett AM, Didigu CA, Wilen CB, Malani N, Male F, Lee FH, Bushman FD, Cherry S, Doms RW, Bates P, Briley K. The Major Cellular Sterol Regulatory Pathway Is Required for Andes Virus Infection. PLOS Pathogens 2014, 10: e1003911. PMID: 24516383, PMCID: PMC3916400, DOI: 10.1371/journal.ppat.1003911.Peer-Reviewed Original ResearchConceptsRegulatory pathwaysHuman haploid cellsParallel genetic screensGenetic screenPathogenic New World hantavirusesGenomic screenAndes virusHaploid cellsGene disruptionRNA interferenceANDV entryDeficient cellsCellular requirementsCellular cholesterolRNA virusesANDV infectionLarge familyPharmacologic inhibitionWorldwide distributionAndes Virus InfectionNew World hantavirusesVirus bindingPathwayHost factorsSterol synthesis