Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/135198
Title: INVESTIGATING THE ROLE OF HYPOXIA IN DENGUE VIRUS INFECTION
Authors: GAN SHUYI, ESTHER
Keywords: Dengue, Hypoxia, Cellular Lipids, Fc Receptors
Issue Date: 16-Jan-2017
Citation: GAN SHUYI, ESTHER (2017-01-16). INVESTIGATING THE ROLE OF HYPOXIA IN DENGUE VIRUS INFECTION. ScholarBank@NUS Repository.
Abstract: Dengue virus (DENV) has been found to replicate in lymphoid organs, such as lymph nodes and the spleen, as well as the liver in post mortem examination. These organs have environments with low oxygen levels (lymphoid organs -0.5-4.5% 0xygen, liver -5% 0xygen) compared to atmospheric air (-20% 0xygen) due to the vascular anatomy. Here we show that monocytes adapted to 3% 02 exhibit differences in susceptibility to infection, especially with antibody-opsonized DENV. We found that under hypoxic conditions, monocytes upregulate FcyRIIA in a HIF1a-dependent manner, resulting in enhanced antibody-opsonized DENV infection in monocytic cells. However, chemical stabilization of HIF1a only resulted in increased binding of antibody-opsonized DENV but not entry. Instead, a HIF1a independent but hypoxia driven increase in membrane ether lipid concentrations is required to complement the increased expression of FcyRIIA for enhanced antibody-dependent entry. Indeed reducing ether lipids in hypoxic cells reversed enhanced DENV infection without altering FcyRIIA expression. Our findings thus indicate that the increased viral burden associated with secondary DENV infection is thus antibody-dependent but hypoxia-mediated. Collectively, we have shown that physiological oxygen tension affects DENV infections by altering FcyRIIA expression and host membrane lipid compositions.
URI: http://scholarbank.nus.edu.sg/handle/10635/135198
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