한빛사논문
Abstract
Seong-Jun Kim1,†,*, Jae Young Jang2,†*, Eun-Jung Kim1, Eun Kyung Cho2, Dae Gyun Ahn1, Chonsaeng Kim1, Han Seul Park2, Soung Won Jeong2, Sae Hwan Lee3, Sang Gyune Kim4, Young Seok Kim4, Hong Soo Kim3, Boo Sung Kim2, Ji-Hyung Lee5, and Aleem Siddiqui5,6
1 Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Yuseong, Daejeon, South Korea
2 Institute for Digestive Research, Digestive Disease Center, Department of Internal Medicine, College of Medicine, Soonchunhyang University, Seoul, South Korea
3 Department of Internal Medicine, College of Medicine, Soonchunhyang University, Cheonan, South Korea
4 Department of Internal Medicine, College of Medicine, Soonchunhyang University, Bucheon, South Korea
5 Department of Medicine, University of California, San Diego, La Jolla, CA, USA
6 Division of Infectious Diseases, University of California, San Diego, La Jolla, CA, USA
† These authors contributed equally to this work.
*Corresponding authors: Jae Young Jang, MD, PhD, Department of Internal Medicine, College of Medicine, Soonchunhyang University, Yongsan-gu, Seoul 04401, South Korea, Seong-Jun Kim, PhD, Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Yuseong, Daejeon 34114, South Korea.
Abstract
Hepatitis C virus (HCV) alters mitochondrial dynamics associated with persistent viral infection and suppression of innate immunity. Mitochondrial dysfunction is also a pathologic feature of direct-acting antiviral (DAA) treatment. Despite the high efficacy of DAAs, their treatment of patients with chronic hepatitis C in interferon-sparing regimens occasionally produces undesirable side effects such as fatigue, migraine and other conditions, which may be linked to mitochondrial dysfunction. Here we show that clinically prescribed DAAs, including Sofosbuvir, affect mitochondrial dynamics. To counter these adverse effects, we examined HCV- and DAA-induced aberrant mitochondrial dynamics modulated by ginsenoside, which is known to support healthy mitochondrial physiology and the innate immune system. We screened several ginsenoside compounds showing antiviral activity using a robust HCV cell culture system. We investigated the role of ginsenosides in antiviral efficacy, alteration of the mitochondrial transmembrane potential, abnormal mitochondrial fission, its upstream signaling, and mitophagic process caused by HCV infection or DAA treatment. Only One of the compounds, ginsenoside Rg3 (G-Rg3), exhibited the notable and promising anti-HCV potential. Treatment of HCV-infected cells with G-Rg3 increased HCV core protein-mediated reduction in the expression level of cytosolic p21 required for increasing the cyclin-dependent kinase 1 (CDK1) activity, which catalyzes Ser616 phosphorylation of dynamin-related protein 1 (Drp1). The HCV-induced mitophagy, which follows mitochondrial fission, was also rescued by G-Rg3 treatment. CONCLUSIONS: G-Rg3 inhibits HCV propagation. Its antiviral mechanism involves restoring the HCV-induced Drp1-mediated aberrant mitochondrial fission process, thereby resulting in suppression of persistent HCV infection. This article is protected by copyright. All rights reserved.
Keywords: New HCV treatment; Sofosbuvir; Mitochondrial dysfunction
논문정보
관련 링크
연구자 키워드
관련분야 논문보기
해당논문 저자보기