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

TitleDifferential Metabolic Reprogramming by Zika Virus Promotes Cell Death in Human versus Mosquito Cells
Authors
Keywordsapoptosis
AMPK
Zika virus
virus metabolism
Issue Date2019
Citation
Cell Metabolism, 2019, v. 29, n. 5, p. 1206-1216.e4 How to Cite?
Abstract© 2019 Elsevier Inc. 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. Thaker et al. report that Zika virus differentially rewires the metabolism of human cells and mosquito cells during infection and that this differential metabolic rewiring contributes to the cell death observed in Zika-virus-infected human cells and survival in Zika-virus-infected mosquito cells.
Persistent Identifierhttp://hdl.handle.net/10722/285832
ISSN
2019 Impact Factor: 21.567
2015 SCImago Journal Rankings: 11.842
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorThaker, Shivani K.-
dc.contributor.authorChapa, Travis-
dc.contributor.authorGarcia, Gustavo-
dc.contributor.authorGong, Danyang-
dc.contributor.authorSchmid, Ernst W.-
dc.contributor.authorArumugaswami, Vaithilingaraja-
dc.contributor.authorSun, Ren-
dc.contributor.authorChristofk, Heather R.-
dc.date.accessioned2020-08-18T04:56:46Z-
dc.date.available2020-08-18T04:56:46Z-
dc.date.issued2019-
dc.identifier.citationCell Metabolism, 2019, v. 29, n. 5, p. 1206-1216.e4-
dc.identifier.issn1550-4131-
dc.identifier.urihttp://hdl.handle.net/10722/285832-
dc.description.abstract© 2019 Elsevier Inc. 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. Thaker et al. report that Zika virus differentially rewires the metabolism of human cells and mosquito cells during infection and that this differential metabolic rewiring contributes to the cell death observed in Zika-virus-infected human cells and survival in Zika-virus-infected mosquito cells.-
dc.languageeng-
dc.relation.ispartofCell Metabolism-
dc.subjectapoptosis-
dc.subjectAMPK-
dc.subjectZika virus-
dc.subjectvirus metabolism-
dc.titleDifferential Metabolic Reprogramming by Zika Virus Promotes Cell Death in Human versus Mosquito Cells-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1016/j.cmet.2019.01.024-
dc.identifier.pmid30827860-
dc.identifier.pmcidPMC6818653-
dc.identifier.scopuseid_2-s2.0-85062506900-
dc.identifier.volume29-
dc.identifier.issue5-
dc.identifier.spage1206-
dc.identifier.epage1216.e4-
dc.identifier.eissn1932-7420-
dc.identifier.f1000735240309-

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