2022
Restriction of viral replication, rather than T cell immunopathology, drives lethality in MNV CR6-infected STAT1-deficient mice
Sharon A, Filyk H, Fonseca N, Simister R, Filler R, Yuen W, Hardman B, Robinson H, Seo J, Rocha-Pereira J, Welch I, Neyts J, Wilen C, Crowe S, Osborne L. Restriction of viral replication, rather than T cell immunopathology, drives lethality in MNV CR6-infected STAT1-deficient mice. The Journal Of Immunology 2022, 208: 182.04-182.04. DOI: 10.4049/jimmunol.208.supp.182.04.Peer-Reviewed Original ResearchAntiviral T cell responsesT cell responsesSTAT1-deficient miceCell responsesViral replicationViral infectionViral-induced tissue damageC57BL6/J miceAdaptive immune populationsLimited viral replicationT cell immunopathologyAdaptive immune cellsUncontrolled viral replicationHigh viral loadHost-directed mechanismKey innateLethal immunopathologyInfectious insultsViral loadImmune populationsImmune cellsJ miceTherapeutic administrationIntestinal homeostasisIntestinal mucosaRestriction of Viral Replication, Rather than T Cell Immunopathology, Drives Lethality in Murine Norovirus CR6-Infected STAT1-Deficient Mice
Sharon AJ, Filyk HA, Fonseca NM, Simister RL, Filler RB, Yuen W, Hardman BK, Robinson HG, Seo JH, Rocha-Pereira J, Welch I, Neyts J, Wilen CB, Crowe SA, Osborne LC. Restriction of Viral Replication, Rather than T Cell Immunopathology, Drives Lethality in Murine Norovirus CR6-Infected STAT1-Deficient Mice. Journal Of Virology 2022, 96: e02065-21. PMID: 35107369, PMCID: PMC8941907, DOI: 10.1128/jvi.02065-21.Peer-Reviewed Original ResearchConceptsAntiviral T cell responsesT cell responsesSTAT1-deficient miceSystemic viral infectionCell responsesViral replicationViral infectionTissue damageViral-induced tissue damageVirus-induced tissue damageAltered T-cell responsesLimited viral replicationT cell immunopathologyOngoing inflammatory responseAdaptive immune cellsUncontrolled viral replicationBreakdown of toleranceImmune-mediated pathologyHost-directed mechanismViral componentsAntiviral CD4Lethal immunopathologyInfectious insultsImmune activationImmunological tolerance
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 replicationNonsteroidal Anti-inflammatory Drugs Dampen the Cytokine and Antibody Response to SARS-CoV-2 Infection
Chen JS, Alfajaro MM, Chow RD, Wei J, Filler RB, Eisenbarth SC, Wilen CB. Nonsteroidal Anti-inflammatory Drugs Dampen the Cytokine and Antibody Response to SARS-CoV-2 Infection. Journal Of Virology 2021, 95: 10.1128/jvi.00014-21. PMID: 33441348, PMCID: PMC8092681, DOI: 10.1128/jvi.00014-21.Peer-Reviewed Original ResearchSARS-CoV-2 infectionNonsteroidal anti-inflammatory drugsCOVID-19 pathogenesisSARS-CoV-2Anti-inflammatory drugsProduction of prostaglandinsCyclooxygenase-2Immune responseNSAID treatmentCyclooxygenase-1Enzymes cyclooxygenase-1Inflammatory responseAbility of NSAIDsAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionSyndrome coronavirus 2 infectionSARS-CoV-2 vaccinationViral replicationPro-inflammatory cytokine responseCoronavirus 2 infectionExpression of angiotensinRelief of painPro-inflammatory cytokinesCoronavirus disease 2019 (COVID-19) pandemicHumoral immune response
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