Please use this identifier to cite or link to this item: https://doi.org/10.1128/JVI.00617-17
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dc.titleTranscriptional profiling confirms the therapeutic effects of mast cell stabilization in a dengue disease model
dc.contributor.authorMorrison J.
dc.contributor.authorRathore A.P.S.
dc.contributor.authorMantri C.K.
dc.contributor.authorAman S.A.B.
dc.contributor.authorNishida A.
dc.contributor.authorSt. John A.L.
dc.date.accessioned2020-09-09T04:17:20Z
dc.date.available2020-09-09T04:17:20Z
dc.date.issued2017
dc.identifier.citationMorrison J., Rathore A.P.S., Mantri C.K., Aman S.A.B., Nishida A., St. John A.L. (2017). Transcriptional profiling confirms the therapeutic effects of mast cell stabilization in a dengue disease model. Journal of Virology 91 (18) : e00617-17. ScholarBank@NUS Repository. https://doi.org/10.1128/JVI.00617-17
dc.identifier.issn0022-538X
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/175152
dc.description.abstractThere are no approved therapeutics for the treatment of dengue disease despite the global prevalence of dengue virus (DENV) and its mosquito vectors. DENV infections can lead to vascular complications, hemorrhage, and shock due to the ability of DENV to infect a variety of immune and nonimmune cell populations. Increasingly, studies have implicated the host response as a major contributor to severe disease. Inflammatory products of various cell types, including responding T cells, mast cells (MCs), and infected monocytes, can contribute to immune pathology. In this study, we show that the host response to DENV infection in immunocompetent mice recapitulates transcriptional changes that have been described in human studies. We found that DENV infection strongly induced metabolic dysregulation, complement signaling, and inflammation. DENV also affected the immune cell content of the spleen and liver, enhancing NK, NKT, and CD8+ T cell activation. The MCstabilizing drug ketotifen reversed many of these responses without suppressing memory T cell formation and induced additional changes in the transcriptome and immune cell composition of the spleen, consistent with reduced inflammation. This study provides a global transcriptional map of immune activation in DENV target organs of an immunocompetent host and supports the further development of targeted immunomodulatory strategies to treat DENV disease. © 2017 American Society for Microbiology.
dc.publisherAmerican Society for Microbiology
dc.sourceUnpaywall 20200831
dc.subjectantiallergic agent
dc.subjectketotifen
dc.subjectanimal
dc.subjectdengue
dc.subjectDengue virus
dc.subjectdisease model
dc.subjectgene expression profiling
dc.subjectimmunology
dc.subjectmast cell
dc.subjectmouse
dc.subjectpathology
dc.subjectAnimals
dc.subjectAnti-Allergic Agents
dc.subjectDengue
dc.subjectDengue Virus
dc.subjectDisease Models, Animal
dc.subjectGene Expression Profiling
dc.subjectKetotifen
dc.subjectMast Cells
dc.subjectMice
dc.typeArticle
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.description.doi10.1128/JVI.00617-17
dc.description.sourcetitleJournal of Virology
dc.description.volume91
dc.description.issue18
dc.description.pagee00617-17
dc.published.statePublished
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