ChREBP, a glucose-responsive transcriptional factor, enhances glucose metabolism to support biosynthesis in human cytomegalovirus-infected cells.
Carbohydrate-response element binding protein (ChREBP) plays a key role in regulating glucose metabolism and de novo lipogenesis in metabolic tissues and cancer cells. Here we report that ChREBP is also a critical regulator of the metabolic alterations induced during human cytomegalovirus (HCMV) infection. The expression of both ChREBP-α and ChREBP-β is robustly induced in HCMV-infected human fibroblasts; this induction is required for efficient HCMV infection. Depletion of ChREBP in HCMV-infected cells results in reduction of HCMV-induced glucose transporter 4 and glucose transporter 2 expression, leading to inhibition of glucose uptake, lactate production, nucleotide biosynthesis, and NADPH generation. We previously reported that HCMV infection induces lipogenesis through the activation of sterol regulatory element binding protein 1, which is mediated by the induction of PKR-like endoplasmic reticulum kinase. Data from the present study show that HCMV-induced lipogenesis is also controlled by the induction of ChREBP, in a second mechanism involved in the regulation of HCMV-induced de novo lipogenesis. These results suggest that ChREBP plays a key role in reprogramming glucose and lipid metabolism in HCMV infection.
Department of Cancer Biology, Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Yongjun
Y
Yu
Tobi G
TG
Maguire
James C
JC
Alwine
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D003587:Cytomegalovirus / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000821:virology; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology*; D006801:Humans; D050155:Lipogenesis / Q000187:drug effects*; D008297:Male; D008954:Models, Biological; D009711:Nucleotides / Q000096:biosynthesis*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D019892:eIF-2 Kinase / Q000378:metabolism
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D005947:Glucose; D009711:Nucleotides; D020033:Protein Isoforms; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D019892:eIF-2 Kinase; C116385:MLXIPL protein, human
glycolysis; lipid synthesis; viral pathogenesis