2021
A stem-loop RNA RIG-I agonist protects against acute and chronic SARS-CoV-2 infection in mice
Mao T, Israelow B, Lucas C, Vogels CBF, Gomez-Calvo ML, Fedorova O, Breban MI, Menasche BL, Dong H, Linehan M, Alpert T, Anderson F, Earnest R, Fauver J, Kalinich C, Munyenyembe K, Ott I, Petrone M, Rothman J, Watkins A, Wilen C, Landry M, Grubaugh N, Pyle A, Iwasaki A. A stem-loop RNA RIG-I agonist protects against acute and chronic SARS-CoV-2 infection in mice. Journal Of Experimental Medicine 2021, 219: e20211818. PMID: 34757384, PMCID: PMC8590200, DOI: 10.1084/jem.20211818.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionChronic SARS-CoV-2 infectionVariants of concernLethal SARS-CoV-2 infectionPost-infection therapyLower respiratory tractPost-exposure treatmentType I interferonSARS-CoV-2Effective medical countermeasuresAdaptive immune systemBroad-spectrum antiviralsContext of infectionSingle doseRespiratory tractViral controlImmunodeficient miceSevere diseaseMouse modelI interferonViral infectionImmune systemInnate immunityDisease preventionConsiderable efficacyTranslational shutdown and evasion of the innate immune response by SARS-CoV-2 NSP14 protein
Hsu JC, Laurent-Rolle M, Pawlak JB, Wilen CB, Cresswell P. Translational shutdown and evasion of the innate immune response by SARS-CoV-2 NSP14 protein. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2101161118. PMID: 34045361, PMCID: PMC8214666, DOI: 10.1073/pnas.2101161118.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Interferon-stimulated genesImmune responseSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Host protein synthesisRespiratory syndrome coronavirus 2Syndrome coronavirus 2Innate immune responseUnprecedented global health crisisCoronavirus 2N7-methyltransferase activityOngoing COVID-19 pandemicHuman coronavirusesTranslational shutdownVirus replicationNsp14 proteinGlobal health crisisProtein synthesisInhibition activityCausative agentCOVID-19COVID-19 pandemicSARS-CoV-2 nsp14Dependent inductionSingle-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 replicationNorovirus evolution in immunodeficient mice reveals potentiated pathogenicity via a single nucleotide change in the viral capsid
Walker FC, Hassan E, Peterson ST, Rodgers R, Schriefer LA, Thompson CE, Li Y, Kalugotla G, Blum-Johnston C, Lawrence D, McCune BT, Graziano VR, Lushniak L, Lee S, Roth AN, Karst SM, Nice TJ, Miner JJ, Wilen CB, Baldridge MT. Norovirus evolution in immunodeficient mice reveals potentiated pathogenicity via a single nucleotide change in the viral capsid. PLOS Pathogens 2021, 17: e1009402. PMID: 33705489, PMCID: PMC7987144, DOI: 10.1371/journal.ppat.1009402.Peer-Reviewed Original ResearchConceptsNucleotide changesSingle nucleotide changeViral capsidAmino acid changesEvolutionary potentialIFN-competent hostsIntestinal myeloid cellsSelective pressureSingle nucleotideKey controllerNorovirus evolutionAcid changesLethal pathogenVirus growthEnhanced virulenceMice revealsIFN responseHigh replicationEnhanced recruitmentMyeloid cellsExtraintestinal disseminationIntestinal replicationReplicationPathogenicityCapsidCD300lf Conditional Knockout Mouse Reveals Strain-Specific Cellular Tropism of Murine Norovirus
Graziano VR, Alfajaro MM, Schmitz CO, Filler RB, Strine MS, Wei J, Hsieh LL, Baldridge MT, Nice TJ, Lee S, Orchard RC, Wilen CB. CD300lf Conditional Knockout Mouse Reveals Strain-Specific Cellular Tropism of Murine Norovirus. Journal Of Virology 2021, 95: 10.1128/jvi.01652-20. PMID: 33177207, PMCID: PMC7925115, DOI: 10.1128/jvi.01652-20.Peer-Reviewed Original ResearchConceptsConditional knockout miceIntestinal epithelial cellsCell tropismKnockout miceTuft cellsDendritic cellsMyelomonocytic cellsB cellsCellular tropismMurine norovirusEpithelial cellsViral RNA levelsInnate immune responseCause of gastroenteritisMNoV infectionCell typesViral loadGastrointestinal infectionsReceptor expressionImmunocompetent humansImmune responseCell type-specific rolesMouse modelIntestinal tissueMNoV
2019
Mouse Norovirus Infection Arrests Host Cell Translation Uncoupled from the Stress Granule-PKR-eIF2α Axis
Fritzlar S, Aktepe TE, Chao YW, Kenney ND, McAllaster MR, Wilen CB, White PA, Mackenzie JM. Mouse Norovirus Infection Arrests Host Cell Translation Uncoupled from the Stress Granule-PKR-eIF2α Axis. MBio 2019, 10: 10.1128/mbio.00960-19. PMID: 31213553, PMCID: PMC6581855, DOI: 10.1128/mbio.00960-19.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCaliciviridae InfectionsCytoplasmic GranulesDNA HelicasesEIF-2 KinaseEukaryotic Initiation Factor-2Host-Pathogen InteractionsImmune EvasionImmunity, InnateMicePhosphorylationPoly-ADP-Ribose Binding ProteinsProtein BiosynthesisRNA HelicasesRNA Recognition Motif ProteinsViral ProteinsVirus ReplicationConceptsIntegrated stress responseProtein kinase RStress granulesProtein translationCellular homeostasisProtein G3BP1Host translationCytoplasmic RNA granulesMNV replication complexHijack host machineryPhosphorylation of eIF2αHost protein translationCellular response systemsHost cell translationEukaryotic initiation factorMNV infectionPhosphorylated eukaryotic initiation factorRNA granulesTranslational controlSG formationInitiation factorsSG nucleationTranslational arrestHost machineryVirus replication
2017
Norovirus Cell Tropism Is Determined by Combinatorial Action of a Viral Non-structural Protein and Host Cytokine
Lee S, Wilen CB, Orvedahl A, McCune BT, Kim KW, Orchard RC, Peterson ST, Nice TJ, Baldridge MT, Virgin HW. Norovirus Cell Tropism Is Determined by Combinatorial Action of a Viral Non-structural Protein and Host Cytokine. Cell Host & Microbe 2017, 22: 449-459.e4. PMID: 28966054, PMCID: PMC5679710, DOI: 10.1016/j.chom.2017.08.021.Peer-Reviewed Original ResearchConceptsIntestinal epithelial cellsViral surface proteinsCellular tropismPersistent viral infectionNon-structural protein NS1Expression of NS1MNoV infectionSurface proteinsHost cytokinesAntiviral immunityHost determinantsInterferon lambdaViral infectionKey host determinantsViral non-structural proteinsCell tropismFecal sheddingNon-structural proteinsTropism determinantsEpithelial cellsGlobal causeInfectionTropismProtein NS1MNoVViral Replication Complexes Are Targeted by LC3-Guided Interferon-Inducible GTPases
Biering SB, Choi J, Halstrom RA, Brown HM, Beatty WL, Lee S, McCune BT, Dominici E, Williams LE, Orchard RC, Wilen CB, Yamamoto M, Coers J, Taylor GA, Hwang S. Viral Replication Complexes Are Targeted by LC3-Guided Interferon-Inducible GTPases. Cell Host & Microbe 2017, 22: 74-85.e7. PMID: 28669671, PMCID: PMC5591033, DOI: 10.1016/j.chom.2017.06.005.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutophagyCaliciviridae InfectionsCarrier ProteinsCell LineCytosolFemaleFibroblastsGene Knockdown TechniquesGTP PhosphohydrolasesHeLa CellsHumansImmunity, InnateInterferon-gammaInterferonsMacrophagesMaleMiceMice, Inbred C57BLMicrotubule-Associated ProteinsNorovirusRAW 264.7 CellsVacuolesViral Plaque AssayVirus ReplicationConceptsViral replication complexReplication complexImmunity-related GTPasesGuanylate-binding proteinsIFN-inducible GTPasesMNV replication complexPositive-sense RNA genomeLC3 conjugation systemConjugation systemInterferon-inducible GTPasesMembranes of vacuolesAutophagy proteinsRNA genomeGTPasesDiverse pathogensMNV replicationHuman cellsAdvantageous microenvironmentImmune defense mechanismsMembranous structuresDefense mechanismsMurine norovirusHost immune systemMembrane structureProtein
2016
Homeostatic Control of Innate Lung Inflammation by Vici Syndrome Gene Epg5 and Additional Autophagy Genes Promotes Influenza Pathogenesis
Lu Q, Yokoyama CC, Williams JW, Baldridge MT, Jin X, DesRochers B, Bricker T, Wilen CB, Bagaitkar J, Loginicheva E, Sergushichev A, Kreamalmeyer D, Keller BC, Zhao Y, Kambal A, Green DR, Martinez J, Dinauer MC, Holtzman MJ, Crouch EC, Beatty W, Boon AC, Zhang H, Randolph GJ, Artyomov MN, Virgin HW. Homeostatic Control of Innate Lung Inflammation by Vici Syndrome Gene Epg5 and Additional Autophagy Genes Promotes Influenza Pathogenesis. Cell Host & Microbe 2016, 19: 102-113. PMID: 26764600, PMCID: PMC4714358, DOI: 10.1016/j.chom.2015.12.011.Peer-Reviewed Original ResearchConceptsAutophagy genesLung inflammationGene functionLethal influenza virus infectionBone marrow transplantation experimentsInnate immune inflammationInfluenza virus infectionEPG5Transplantation experimentsNormal homeostatic mechanismsHomeostatic controlInflammation supportLung transcriptomicsImmune inflammationRecurrent infectionsCytokine expressionInfluenza pathogenesisPulmonary abnormalitiesGenesInflammation resultsVirus infectionInfluenza resistanceElevated baselineHomeostatic mechanismsLung physiology