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Differential Metabolic Reprogramming by Zika Virus Promotes Cell Death in Human versus Mosquito Cells.

Abstract：

: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.

journal_name

Cell Metab

journal_title

Cell metabolism

authors

Thaker SK,Chapa T,Garcia G Jr,Gong D,Schmid EW,Arumugaswami V,Sun R,Christofk HR

doi

10.1016/j.cmet.2019.01.024

subject

Has Abstract

pub_date

2019-05-07 00:00:00

pages

1206-1216.e4

issue

5

eissn

1550-4131

issn

1932-7420

pii

S1550-4131(19)30064-6

journal_volume

29

pub_type

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