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https://doi.org/10.1016/j.celrep.2021.110118
Title: | Dysregulated metabolism underpins Zika-virus-infection-associated impairment in fetal development | Authors: | Yau, Clement Low, John Z. H. Gan, Esther S. Kwek, Swee Sen Cui, Liang Tan, Hwee Cheng Mok, Darren Z. L. Chan, Candice Y. Y. Sessions, October M. Watanabe, Satoru Vasudevan, Subhash G. Lee, Yie Hou Chan, Kuan Rong Ooi, Eng Eong |
Keywords: | attenuated congenital zika syndrome glycolysis pathogenic pyruvate supplementation tricarboxylic acid cycle Zika virus |
Issue Date: | 1-Dec-2021 | Publisher: | Elsevier B.V. | Citation: | Yau, Clement, Low, John Z. H., Gan, Esther S., Kwek, Swee Sen, Cui, Liang, Tan, Hwee Cheng, Mok, Darren Z. L., Chan, Candice Y. Y., Sessions, October M., Watanabe, Satoru, Vasudevan, Subhash G., Lee, Yie Hou, Chan, Kuan Rong, Ooi, Eng Eong (2021-12-01). Dysregulated metabolism underpins Zika-virus-infection-associated impairment in fetal development. Cell Reports 37 (11) : 110118. ScholarBank@NUS Repository. https://doi.org/10.1016/j.celrep.2021.110118 | Rights: | Attribution-NonCommercial-NoDerivatives 4.0 International | Abstract: | Zika virus (ZIKV) is an Aedes-mosquito-borne flavivirus that causes debilitating congenital and developmental disorders. Improved understanding of ZIKV pathogenesis could assist efforts to fill the therapeutic and vaccine gap. We use several ZIKV strains, including a pair differing by a single phenylalanine-to-leucine substitution (M-F37L) in the membrane (M) protein, coupled with unbiased genomics to demarcate the border between attenuated and pathogenic infection. We identify infection-induced metabolic dysregulation as a minimal set of host alterations that differentiates attenuated from pathogenic ZIKV strains. Glycolytic rewiring results in impaired oxidative phosphorylation and mitochondrial dysfunction that trigger inflammation and apoptosis in pathogenic but not attenuated ZIKV strains. Critically, pyruvate supplementation prevents cell death, in vitro, and rescues fetal development in ZIKV-infected dams. Our findings thus demonstrate dysregulated metabolism as an underpinning of ZIKV pathogenicity and raise the potential of pyruvate supplementation in expectant women as a prophylaxis against congenital Zika syndrome. © 2021 The Authors | Source Title: | Cell Reports | URI: | https://scholarbank.nus.edu.sg/handle/10635/231881 | ISSN: | 2211-1247 | DOI: | 10.1016/j.celrep.2021.110118 | Rights: | Attribution-NonCommercial-NoDerivatives 4.0 International |
Appears in Collections: | Elements Staff Publications |
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