Glycolysis is reduced in dengue virus 2 infected liver cells
Issued Date
2024-12-01
Resource Type
eISSN
20452322
Scopus ID
2-s2.0-85189896268
Journal Title
Scientific Reports
Volume
14
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Scientific Reports Vol.14 No.1 (2024)
Suggested Citation
Chumchanchira C., Ramphan S., Sornjai W., Roytrakul S., Lithanatudom P., Smith D.R. Glycolysis is reduced in dengue virus 2 infected liver cells. Scientific Reports Vol.14 No.1 (2024). doi:10.1038/s41598-024-58834-w Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/97986
Title
Glycolysis is reduced in dengue virus 2 infected liver cells
Corresponding Author(s)
Other Contributor(s)
Abstract
Infections with dengue virus (DENV) remain a worldwide public health problem. A number of bona fide cellular targets of DENV have been identified including liver cells. Despite the many lines of evidence confirming the involvement of hepatocytes during DENV infection, only a few studies have used proteomic analysis to understand the modulation of the cellular proteome occurring upon DENV infection. We utilized a 2D-gel electrophoresis analysis to identify proteins that were differentially regulated by DENV 2 infection of liver (Hep3B) cells at 12 h post infection (hpi) and at 48 hpi. The analysis identifies 4 proteins differentially expressed at 12 hpi, and 14 differentially regulated at 48 hpi. One candidate protein identified as downregulated at 48 hpi in the proteomic analysis (GAPDH) was validated in western blotting in Hep3B cells, and subsequently in induced pluripotent stem cell (iPSC) derived human hepatocytes. The reduced expression of GAPDH was coupled with an increase in NADH, and a significantly reduced NAD + /NADH ratio, strongly suggesting that glycolysis is down regulated in response to DENV 2 infection. Metformin, a well characterized drug used in the treatment of diabetes mellitus, is an inhibitor of hepatic gluconeogenesis was shown to reduce the level of DENV 2 infection and new virus production. Collectively these results show that although glycolysis is reduced, glucose is still required, possibly for use by the pentose phosphate pathway to generate nucleosides required for viral replication.