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Title: Transcriptional profiling confirms the therapeutic effects of mast cell stabilization in a dengue disease model
Authors: Morrison J.
Rathore A.P.S. 
Mantri C.K. 
Aman S.A.B. 
Nishida A.
St. John A.L. 
Keywords: antiallergic agent
Dengue virus
disease model
gene expression profiling
mast cell
Anti-Allergic Agents
Dengue Virus
Disease Models, Animal
Gene Expression Profiling
Mast Cells
Issue Date: 2017
Publisher: American Society for Microbiology
Citation: Morrison 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.
Abstract: There 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.
Source Title: Journal of Virology
ISSN: 0022-538X
DOI: 10.1128/JVI.00617-17
Appears in Collections:Staff Publications

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