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

Cell metabolism | 2019

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.

Pubmed ID: 30827860 RIS Download

Associated grants

  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM008042
  • Agency: NCI NIH HHS, United States
    Id: T32 CA009120
  • Agency: NCI NIH HHS, United States
    Id: T32 CA009056
  • Agency: NIAID NIH HHS, United States
    Id: T32 AI060567
  • Agency: NCI NIH HHS, United States
    Id: R01 CA215185
  • Agency: NIAMS NIH HHS, United States
    Id: R01 AR070245

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This is a list of tools and resources that we have found mentioned in this publication.


Zika virus Envelope protein antibody (antibody)

RRID:AB_2747413

This polyclonal targets Zika virus Envelope protein

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Acetyl-CoA Carboxylase 1 Antibody (antibody)

RRID:AB_10547752

This polyclonal targets Acetyl-CoA Carboxylase 1

View all literature mentions

Caspase-3 Antibody (antibody)

RRID:AB_331439

This polyclonal targets Caspase-3

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β-Actin (8H10D10) Mouse mAb (antibody)

RRID:AB_2242334

This monoclonal targets beta-actin

View all literature mentions

Monoclonal Anti-alpha-Tubulin antibody produced in mouse (antibody)

RRID:AB_477582

This monoclonal targets alpha-Tubulin antibody produced in mouse

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ATC-15 (cell line)

RRID:CVCL_Z223

Cell line ATC-15 is a Spontaneously immortalized cell line with a species of origin Aedes albopictus (Asian tiger mosquito)

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C6/36 (cell line)

RRID:CVCL_Z230

Cell line C6/36 is a Spontaneously immortalized cell line with a species of origin Aedes albopictus (Asian tiger mosquito)

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ATC-10 (cell line)

RRID:CVCL_Z222

Cell line ATC-10 is a Spontaneously immortalized cell line with a species of origin Aedes aegypti (Yellowfever mosquito)

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Vero (cell line)

RRID:CVCL_0059

Cell line Vero is a Spontaneously immortalized cell line with a species of origin Chlorocebus sabaeus

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HFF-1 (cell line)

RRID:CVCL_3285

Cell line HFF-1 is a Finite cell line with a species of origin Homo sapiens (Human)

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