期刊
CELL METABOLISM
卷 29, 期 5, 页码 1206-+出版社
CELL PRESS
DOI: 10.1016/j.cmet.2019.01.024
关键词
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资金
- UCLA Virology and Gene Therapy Training Grant [T32AI060567]
- UCLA Tumor Immunology Training Grant (USHHS Ruth L. Kirschstein Institutional National Research Service Award) [T32 CA009056]
- American Cancer Society [RSG-16-111-01-MPC]
- NIH/NCI [RO1 CA215185-01]
- UCLA Jonsson Comprehensive Cancer Center
- Eli and Edythe Broad Center for Regenerative Medicine Ablon Scholars Program
- California Institute for Regenerative Medicine (CIRM) award [DISC2-10188]
Zika virus is a pathogen that poses serious consequences, including congenital microcephaly. Although many viruses reprogram host cell metabolism, whether Zika virus alters cellular metabolism and the functional consequences of Zika-induced metabolic changes remain unknown. Here, we show that Zika virus infection differentially reprograms glucose metabolism in human versus C6/36 mosquito cells by increasing glucose use in the tricarboxylic acid cycle in human cells versus increasing glucose use in the pentose phosphate pathway in mosquito cells. Infection of human cells selectively depletes nucleotide triphosphate levels, leading to elevated AMP/ATP ratios, AMP-activated protein kinase (AMPK) phosphorylation, and caspase-mediated cell death. AMPK is also phosphorylated in Zika virus-infected mouse brain. Inhibiting AMPK in human cells decreases Zika virus-mediated cell death, whereas activating AMPK in mosquito cells promotes Zika virus-mediated cell death. These findings suggest that the differential metabolic reprogramming during Zika virus infection of human versus mosquito cells determines whether cell death occurs.
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