Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/155246
Title: Role of glycolysis in myeloid cells during dengue infection
Authors: Loy, Thomas
Keywords: Science::Biological sciences::Microbiology::Virology
Issue Date: 2021
Publisher: Nanyang Technological University
Source: Loy, T. (2021). Role of glycolysis in myeloid cells during dengue infection. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/155246
Abstract: There is no dengue virus (DENV) specific treatment, while there are several issues with the current dengue vaccines. Amongst blood cells, monocytes are the main target of DENV and monocytes interact with non-structural 1 (NS1) protein via TLR2/TLR4/TLR6 that might contribute to pathogenesis by supporting DENV replication and secreting inflammatory cytokines. Since DENV replication and induction of inflammatory cytokines in monocytes depend on glycolysis, we hypothesize that DENV induces metabolic rewiring in monocytes and targeting would ameliorate DENV pathogenesis. We show that in vitro DENV- infected monocytes upregulate glycolysis and inhibiting with 2-deoxy glucose (2DG) reduced DENV replication and production of TNF-α. Bioenergetics and RNAseq demonstrated induction of glycolysis in monocytes of thrombocytopenic patients. In vivo mouse experiments showed 2DG enhancing survival and lessens weight loss. 2DG also altered frequencies of classical and non-classical monocytes and reduces cytokine production from intermediate monocytes. Our study raises the possibility of altering host metabolism to treat DENV infection.
URI: https://hdl.handle.net/10356/155246
DOI: 10.32657/10356/155246
Rights: This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).
Fulltext Permission: open
Fulltext Availability: With Fulltext
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