Gondwanaland
Senior Member
- Messages
- 5,095
FULL TEXT
Proc Natl Acad Sci U S A. 2014 Feb 4;111(5):1951-6. doi: 10.1073/pnas.1310779111. Epub 2014 Jan 21.
ChREBP, a glucose-responsive transcriptional factor, enhances glucose metabolism to support biosynthesis in human cytomegalovirus-infected cells.
Abstract
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.
KEYWORDS:
glycolysis; lipid synthesis; viral pathogenesis
PMID: 24449882 PMCID: PMC3918764 DOI: 10.1073/pnas.1310779111
the above is an interesting explanation and probably valid for a number of infections.
Proc Natl Acad Sci U S A. 2014 Feb 4;111(5):1951-6. doi: 10.1073/pnas.1310779111. Epub 2014 Jan 21.
ChREBP, a glucose-responsive transcriptional factor, enhances glucose metabolism to support biosynthesis in human cytomegalovirus-infected cells.
Abstract
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.
KEYWORDS:
glycolysis; lipid synthesis; viral pathogenesis
PMID: 24449882 PMCID: PMC3918764 DOI: 10.1073/pnas.1310779111
SIGNIFICANCE
Human cytomegalovirus (HCMV)-infected cells and tumor cells produce similar alterations in glucose metabolism, including increasing glucose uptake and glycolysis and redirecting glucose carbon to support synthesis of biomolecules. We show that HCMV infection induces the glucose-responsive transcriptional factor carbohydrate-response element binding protein to reprogram glucose metabolism to support lipid and nucleotide synthesis. This study provides insight into viral mechanisms of pathogenesis.
@Lolinda @picante @Sidereal...
Studies in recent years have shown that HCMV infection can induce dramatic changes in glucose and glutamine metabolism (2–4). HCMV-infected cells have a much higher rate of glycolysis (2), owing largely to the significant induction of glucose transporter (GLUT) 4 to increase glucose uptake (5). Unlike normal cells, the increased glucose flux in HCMV-infected cells is not used for energy production in the tricarboxylic acid (TCA) cycle; instead, a large amount of glucose-derived carbon supports lipid biosynthesis, which is essential for the viral infection (3). Our recent studies have shown that the increased lipid biosynthesis is mediated by the transcriptional factor sterol regulatory element binding protein 1 (SREBP1), which is activated by the induction of PKR-like endoplasmic reticulum kinase (PERK) in HCMV-infected cells (6, 7).
...
the above is an interesting explanation and probably valid for a number of infections.