In vitrohepatitis C virus infection and hepatic choline metabolism

Abstract

Choline is an essential nutrient required for normal neuronal and muscular development, as well as homeostatic regulation of hepatic metabolism. In the liver, choline is incorporated into the main eukaryotic phospholipid, phosphatidylcholine (PC) and can enter one carbon metabolism via mitochondrial oxidation. Hepatitis C virus (HCV) is a hepatotropic positive-strand RNA virus that similar to other positive-strand RNA viruses can impact phospholipid metabolism. In the current study we sought to interrogate the link between choline transport and early HCV infection. Namely, we aimed to investigate how HCV modulates markers of choline metabolism following in vitro infection, while subsequently assessing how the inhibition of choline uptake and metabolism upon concurrent HCV infection may alter early viral replication. Finally, we assessed whether these parameters were consistent between cells cultured in fetal bovine serum (FBS) or human serum (HS), conditions known to differentially affect in vitro HCV infection. We observed that choline transport in FBS-cultured Huh7.5 cells is facilitated by the intermediate affinity transporter choline transporter-like family (CTL), and that CTL1 expression and the incorporation of choline into PC is diminished in 24 h infected FBScultured cells. Reciprocally, limiting the availability of choline for PC synthesis resulted in increased HCV replication at this early stage. In chronically HS-cultured Huh7.5 cells, there were no differences in the expression of choline transporters upon HCV infection or alterations to viral replication when choline transport was inhibited compared to control treatments. However, inhibiting choline uptake and metabolism in this system significantly impaired the production of infectious virions in HS-cultured cells. These results suggest that in addition to a known role of choline kinase, the transport of choline, potentially via CTL1, might also represent an important and regulated process during HCV infection.3

Transcriptome and miRNome Analysis Provide New Insight Into Host Lipid Accumulation, Innate Immunity, and Viral Persistence in Hepatitis C Virus Infection in vitro

“…HCV requires host factors to complete its life cycle, and virus-host factor interaction and host responses to the virus have an impact on host genes and consequently cause HCV-associated liver diseases. Gene expression changes caused by HCV have been widely reported using microarray ( Blackham et al, 2010 ; Liu et al, 2010 ; Woodhouse et al, 2010 ) and disrupted pathways, including lipid metabolism ( Blackham et al, 2010 ; Woodhouse et al, 2010 ), oxidative stress ( Liu et al, 2010 ), and choline metabolism ( Gobeil Odai et al, 2020 ) have been observed. These findings provide partial understanding of the viral pathogenesis, such as steatosis.…”