Anti-adipogenic and antiviral effects of l-carnitine on hepatitis C virus infection.
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 replicon-transfected 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 JFH-1-infected cells with l-carnitine inhibited HCV propagation in a concentration-dependent manner. In contrast, l-carnitine had no anti-HCV activity in the HCV replicon system, which is lacking viral assembly. In addition, l-carnitine did not affect HCV entry. However, l-carnitine 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 HCV-infected hepatocytes. Overall, these results indicated that l-carnitine may be an effective adjunctive agent in antiviral therapies to treat chronic hepatitis C. J. Med. Virol. 89:857-866, 2017. © 2016 Wiley Periodicals, Inc.
Department of Gastroenterology and Hepatology, Hokkaido University, Sapporo, Japan.
Yoko
Y
Tsukuda
Department of Gastroenterology and Hepatology, Hokkaido University, Sapporo, Japan.
Goki
G
Suda
Seiji
S
Tsunematsu
Department of Gastroenterology and Hepatology, Hokkaido University, Sapporo, Japan.
Jun
J
Ito
Department of Gastroenterology and Hepatology, Hokkaido University, Sapporo, Japan.
Fumiyuki
F
Sato
Department of Gastroenterology and Hepatology, Hokkaido University, Sapporo, Japan.
Katsumi
K
Terashita
Department of Gastroenterology and Hepatology, Hokkaido University, Sapporo, Japan.
Masato
M
Nakai
Department of Gastroenterology and Hepatology, Hokkaido University, Sapporo, Japan.
Takuya
T
Sho
Department of Gastroenterology and Hepatology, Hokkaido University, Sapporo, Japan.
Osamu
O
Maehara
Department of Gastroenterology and Hepatology, Hokkaido University, Sapporo, Japan.
Tomoe
T
Shimazaki
Department of Gastroenterology and Hepatology, Hokkaido University, Sapporo, Japan.
Megumi
M
Kimura
Department of Gastroenterology and Hepatology, Hokkaido University, Sapporo, Japan.
Kenichi
K
Morikawa
Department of Gastroenterology and Hepatology, Hokkaido University, Sapporo, Japan.
Mitsuteru
M
Natsuizaka
Department of Gastroenterology and Hepatology, Hokkaido University, Sapporo, Japan.
Koji
K
Ogawa
Department of Gastroenterology and Hepatology, Hokkaido University, Sapporo, Japan.
Shunsuke
S
Ohnishi
Department of Gastroenterology and Hepatology, Hokkaido University, Sapporo, Japan.
Makoto
M
Chuma
Department of Gastroenterology and Hepatology, Hokkaido University, Sapporo, Japan.
Naoya
N
Sakamoto
D019440:Anti-Obesity Agents / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D002331:Carnitine / Q000494:pharmacology*; D002460:Cell Line; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D022781:Hepatocytes / Q000187:drug effects / Q000821:virology; D006801:Humans; D066292:Lipid Droplets / Q000187:drug effects; D019065:Virus Assembly / Q000187:drug effects*
D019440:Anti-Obesity Agents; D000998:Antiviral Agents; D002331:Carnitine
CPT-1; HCV; anti-viral effect; l-carnitine