Please use this identifier to cite or link to this item: https://doi.org/10.15252/embj.201695642
Title: Hypoxia enhances antibody-dependent dengue virus infection
Authors: Gan, Esther Shuyi 
Cheong, Wei Fun 
Chan, Kuan Rong 
Ong, Eugenia Ziying 
Chai, Xiaoran 
Tan, Hwee Cheng 
Ghosh, Sujoy 
Wenk, Markus R 
Ooi, Eng Eong 
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Cell Biology
antibody-dependent enhancement
cellular lipids
dengue
Fc receptors
hypoxia
HEMORRHAGIC-FEVER
CANCER-CELLS
REPLICATION
MACROPHAGES
EXPRESSION
AUTOPHAGY
DISEASE
LIPIDS
ENTRY
MICE
Issue Date: 15-May-2017
Publisher: WILEY
Citation: Gan, Esther Shuyi, Cheong, Wei Fun, Chan, Kuan Rong, Ong, Eugenia Ziying, Chai, Xiaoran, Tan, Hwee Cheng, Ghosh, Sujoy, Wenk, Markus R, Ooi, Eng Eong (2017-05-15). Hypoxia enhances antibody-dependent dengue virus infection. EMBO JOURNAL 36 (10) : 1348-1363. ScholarBank@NUS Repository. https://doi.org/10.15252/embj.201695642
Abstract: © 2017 The Authors. Published under the terms of the CC BY 4.0 license Dengue virus (DENV) has been found to replicate in lymphoid organs such as the lymph nodes, spleen, and liver in post-mortem analysis. These organs are known to have low oxygen levels (~0.5–4.5% O2) due to the vascular anatomy. However, how physiologically low levels of oxygen affect DENV infection via hypoxia-induced changes in the immune response remains unknown. Here, we show that monocytes adapted to 3% O2 show greater susceptibility to antibody-dependent enhancement of DENV infection. Low oxygen level induces HIF1α-dependent upregulation of fragment crystallizable gamma receptor IIA (FcγRIIA) as well as HIF1α-independent alterations in membrane ether lipid concentrations. The increased FcγRIIA expression operates synergistically with altered membrane composition, possibly through increase membrane fluidity, to increase uptake of DENV immune complexes for enhanced infection. Our findings thus indicate that the increased viral burden associated with secondary DENV infection is antibody-dependent but hypoxia-induced and suggest a role for targeting hypoxia-induced factors for anti-dengue therapy.
Source Title: EMBO JOURNAL
URI: https://scholarbank.nus.edu.sg/handle/10635/170271
ISSN: 02614189
14602075
DOI: 10.15252/embj.201695642
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