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Although it is known that DENV infection increases glycolysis, which promotes viral replication, the role of glucose metabolism together with autophagic activity in DENV replication remains unclear. In this study, we reveal that DENV2 infection increased autophagic activity, glucose uptake, protein levels of glucose transporter\u20101 (GLUT1), and glycolysis rate\u2010limiting enzyme hexokinase\u20102 (HK2) in cells. Furthermore, the protein levels of LC3\u2010II and HK2 were increased in the brain tissues of the DENV2\u2010infected suckling mice. However, DENV2 infection decreased ATP level and showed no effect on mRNA expression of HK2 and phosphofructokinase, as well as lactate production, indicating that DENV2\u2010regulated glycolytic flux occurs at the post\u2010transcriptional level and is lactate pathway\u2010independent. Moreover, amiodarone\u2010induced autophagic activity, glucose uptake, HK2 level, and viral titer were reversed by the autophagy inhibitor spautin\u20101 or silencing of <jats:italic>Atg5<\/jats:italic> gene expression. Intriguingly, blocking of glycolysis, HK2 protein level, and viral titer were accordingly decreased, but autophagic activity was increased, suggesting the existence of another regulation mechanism that influences the relationship between glycolysis and autophagy. This is the first report to reveal that DENV2\u2010induced autophagy positively regulates glycolysis and viral replication <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. Our findings open a new avenue wherein metabolic modulation could be used as a target for the treatment of DENV infection.<\/jats:p>","DOI":"10.1002\/kjm2.12271","type":"journal-article","created":{"date-parts":[[2020,8,12]],"date-time":"2020-08-12T09:51:35Z","timestamp":1597225895000},"page":"911-919","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Regulation of autophagy, glucose uptake, and glycolysis under dengue virus infection"],"prefix":"10.1002","volume":"36","author":[{"given":"Ying\u2010Ray","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Medical Research Ditmanson Medical Foundation Chia\u2010Yi Christian Hospital  Chiayi Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan\u2010Ying","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Taipei Medical University  Taipei 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