Anti-Adipogenic and Antiviral Effects of L-Carnitine on Hepatitis C Virus Infection

作者：Tsukuda Yoko; Suda Goki^*; Tsunematsu Seiji; Ito Jun; Sato Fumiyuki; Terashita Katsumi; Nakai Masato; Sho Takuya; Maehara Osamu; Shimazaki Tomoe; Kimura Megumi; Morikawa Kenichi; Natsuizaka Mitsuteru; Ogawa Koji; Ohnishi Shunsuke; Chuma Makoto; Sakamoto Naoya

来源：Journal of Medical Virology, 2017, 89(5): 857-866.

DOI：10.1002/jmv.24692

• HCV
• L-carnitine
• anti-viral effect
• CPT-1

Hepatitis C virus (HCV) has been reported to hijack fatty acid metabolism in infected hepatocytes, taking advantage of lipid droplets for virus assembly. In this study, we analyzed the anti-HCV activity of L-carnitine, a substance involved in the transport of fatty acids into mitochondria. JFH-1 or HCV replicontransfected Huh7.5.1 cells were treated with or without L-carnitine to examine its anti-HCV effects. The effects of L-carnitine on HCV entry, HCV-induced adipogenesis and lipid droplet formation, and HCV-induced oxidative stress were examined. Treatment of JFH1-infected cells with L-carnitine inhibited HCV propagation in a concentration-dependent manner. In contrast, L-carnitine had no antiHCV activity in the HCV replicon system, which is lacking viral assembly. In addition, Lcarnitine did not affect HCV entry. However, Lcarnitine treatment decreased intracellular lipid droplets, which are crucial for HCV assembly in JFH-1-infected cells. The expression level of CPT-1 was decreased in JFH-1-infected cells, and L-carnitine treatment restored this expression. HCV-infected cells exhibited increased production of reactive oxygen species and glutathione oxidation. L-carnitine decreased oxidative stress induced by JFH-1-infection, as shown by glutathione/glutathione disulfide assays and MitoSOX staining. L-carnitine exhibited anti-HCV activity, possibly by inhibiting HCV assembly and through its anti-adipogenic activity in HCV-infected cells. Moreover, L-carnitine has antioxidant properties in HCVinfected hepatocytes. Overall, these results indicated that L-carnitine may be an effective adjunctive agent in antiviral therapies to treat chronic hepatitis C.

• 出版日期2017-5