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Adenovirus E4ORF1-induced MYC activation promotes host cell anabolic glucose metabolism and virus replication.

Abstract：

:Virus infections trigger metabolic changes in host cells that support the bioenergetic and biosynthetic demands of viral replication. Although recent studies have characterized virus-induced changes in host cell metabolism (Munger et al., 2008; Terry et al., 2012), the molecular mechanisms by which viruses reprogram cellular metabolism have remained elusive. Here, we show that the gene product of adenovirus E4ORF1 is necessary for adenovirus-induced upregulation of host cell glucose metabolism and sufficient to promote enhanced glycolysis in cultured epithelial cells by activation of MYC. E4ORF1 localizes to the nucleus, binds to MYC, and enhances MYC binding to glycolytic target genes, resulting in elevated expression of specific glycolytic enzymes. E4ORF1 activation of MYC promotes increased nucleotide biosynthesis from glucose intermediates and enables optimal adenovirus replication in primary lung epithelial cells. Our findings show how a viral protein exploits host cell machinery to reprogram cellular metabolism and promote optimal progeny virion generation.

journal_name

Cell Metab

journal_title

Cell metabolism

authors

Thai M,Graham NA,Braas D,Nehil M,Komisopoulou E,Kurdistani SK,McCormick F,Graeber TG,Christofk HR

doi

10.1016/j.cmet.2014.03.009

subject

Has Abstract

pub_date

2014-04-01 00:00:00

pages

694-701

issue

4

eissn

1550-4131

issn

1932-7420

pii

S1550-4131(14)00113-2

journal_volume

19

pub_type

杂志文章

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