Hepatitis C virus infect ion triggers a tumor-like glutamine metabolism (Hepatology 2016, doi: 10.1002/hep.28949)

報告日期: 2017/03/28
報告時間: 4:00/4:50
報告學生: 廖聰羽(以英文報告)
講評老師: 楊孔嘉
附件下載: 下載[1622-1487729662-1.pdf] 

Hepatitis C Virus Infection Triggers a Tumor-Like Glutamine Metabolism

Pierre L. Levy, Sarah Duponchel, Hannah Eischeid, Jennifer Molle, Maud Michelet, Ga€elle Diserens, Odenthal, Fabien Zoulim, and Birke Bartosch

 HEPATOLOGY, VOL. 00, NO. 00, 2016

Speaker:廖聰羽                                        Date:2017/03/28

Commentator:楊孔嘉老師                                Room : 602


Hepatitis C virus (HCV) is one of the major causes of severe liver diseases including hepatocellular carcinoma (HCC). In spite of recent progress in the development of direct acting antiviral agents, some HCV patients achieving sustained virological response (SVR) are still in the risk of liver fibrosis or even progression to cirrhosis or HCC. Moreover, the molecular mechanisms involved in the progression from chronic HCV infection to HCC are not well established. In this study, the authors provided evidence showing that glutamine metabolism is affected in HCV-infected cells and liver biopsies. HCV infection resulted in increase of transcript levels of glutamine transporters (SLC1A5 and SLC7A5), MYC, and two isoforms (KGA and GAC) of the glutamine catabolism enzyme glutaminase (GLS). The proliferation of HCV-infected cells and the HCV RNA levels were decreased upon depletion of glutamine, and were recovered by supplementation with the tri-carboxylic acid cycle intermediate α-ketoglutarate (α-KG). Similar to glutamine deprivation, treatment with GLS inhibitors or GLS knockdown by short hairpin RNA caused downregulation of HCV replication, which was also restored by α-KG supplementation. Furthermore, inhibiting glutamine metabolism attenuated HCV-induced oxidative stress. Consistently, chronic HCV infection was associated with high transcript levels of key enzymes of glutamine metabolism in liver biopsies. In addition, these transcription levels were positively correlated with fibrosis stages and reduced after antiviral treatment. Therefore, HCV may induce reprogramming of glutamine metabolism to create an environment favorable for viral replication. Drugs targeted to glutamine metabolism may be of therapeutic value to prevent hepatocarcinogenesis in chronic hepatitis C infection.


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