リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

大学・研究所にある論文を検索できる 「Transcription Factor JunB Suppresses Hepatitis C Virus Replication」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

コピーが完了しました

URLをコピーしました

論文の公開元へ論文の公開元へ
書き出し

Transcription Factor JunB Suppresses Hepatitis C Virus Replication

Ariffianto, Adi Deng, Lin Harada, Saki Liang, Yujiao Matsui, Chieko Abe, Takayuki Shoji, Ikuo 神戸大学

2023

概要

We previously reported that hepatitis C virus (HCV) infection activates the reactive oxygen species (ROS)/c-Jun N-terminal kinase (JNK) signaling pathway. Activation of JNK contributes to the development of liver diseases, including metabolic disorders, steatosis, liver cirrhosis and hepatocellular carcioma. JNK is known to have numerous target genes, including JunB, a member of activator protein-1 transcription factor family. Howeve, the roles of JunB in the HCV life cycle and HCV-associated pathogenesis remain unclear. To clarify a physiological role of JunB in HCV infection, we investigated the phosphorylation of JunB in HCV J6/JFH1-infected Huh-7.5 cells. Immunoblot analysis revealed that HCV-induced ROS/JNK activation promoted phosphorylation of JunB. The small interfering RNA (siRNA) knockdown of JunB significantly increased the amount of intracellular HCV RNA as well as the intracellular and extracellular HCV infectivity titers. Conversely, overexpression of JunB significantly reduced the amount of intracellular HCV RNA and the intracellular and extracellular HCV infectivity titers. These results suggest that JunB plays a role in inhibiting HCV propagation. Additonally, HCV-mediated JunB activation promoted hepcidin promoter activity and hepcidin mRNA levels, a key factor in modulating iron homeostasis, suggesting that JunB is involved in HCV-induced transcriptional upregulation of hepcidin. Taken together, we propose that the HCV-induced ROS/JNK/JunB signaling pathway plays roles in inhibiting HCV replication and contributing to HCV-mediated iron metabolism disorder.

この論文で使われている画像

関連論文

参考文献

World Health Organization [Internet]. Hepatitis C. [cited 2023 April 22]. Available from:

https://www.who.int/news-room/fact-sheets/detail/hepatitis-c.

Llovet JM, Zucman-Rossi J, Pikarsky E, Sangro B, Schwartz M, Sherman M, et al. Hepatocellular

carcinoma. Nat Rev Dis Primers. 2016;2:16018.

Vermehren J, Park JS, Jacobson IM, Zeuzem S. Challenges and perspectives of direct antivirals for the

treatment of hepatitis C virus infection. J Hepatol. 2018;69(5):1178–1187.

Heffernan A, Cooke GS, Nayagam S, Thursz M, Hallett TB. Scaling up prevention and treatment towards

the elimination of hepatitis C: a global mathematical model. Lancet. 2019;393(10178):1319–1329.

Scheel TK, Rice CM. Understanding the hepatitis C virus life cycle paves the way for highly effective

therapies. Nat Med. 2013;19(7):837–849.

Deng L, Shoji I, Ogawa W, Kaneda S, Soga T, Jiang DP, et al. Hepatitis C virus infection promotes hepatic

gluconeogenesis through an NS5A-mediated, FoxO1-dependent pathway. J Virol. 2011;85(17):8556–8568.

Deng L, Adachi T, Kitayama K, Bungyoku Y, Kitazawa S, Ishido S, et al. Hepatitis C virus infection

induces apoptosis through a Bax-triggered, mitochondrion-mediated, caspase 3-dependent pathway. J Virol.

2008;82(21):10375–10385.

Deng L, Liang Y, Ariffianto A, Matsui C, Abe T, Muramatsu M, et al. Hepatitis C Virus-Induced ROS/JNK

Signaling Pathway Activates the E3 Ubiquitin Ligase Itch to Promote the Release of HCV Particles via

Polyubiquitylation of VPS4A. J Virol. 2022;96(6):e0181121.

Curran T, Franza BR Jr. Fos and Jun: the AP-1 connection. Cell. 1988;55(3):395–397.

Zeke A, Misheva M, Remenyi A, Bogoyevitch MA. JNK Signaling: Regulation and Functions Based on

Complex Protein-Protein Partnerships. Mol Biol Rev. 2016;80(3):793–835.

Li B, Tournier C, Davis RJ, Flavell RA. Regulation of IL-4 expression by the transcription factor JunB

during T helper cell differentiation. EMBO J. 1999;18(2):420–432.

Shaulian E, Karin M. AP-1 in cell proliferation and survival. Oncogene. 2001;20(19):2390–2400.

Eferl R, Wagner EF. AP-1: a double-edged sword in tumorigenesis. Nat Rev Cancer. 2003;3(11):859–868.

Passegue E, Wagner EF. JunB suppresses cell proliferation by transcriptional activation of p16(INK4a)

expression. EMBO J. 2000;19(12):2969–2979.

Bergman MR, Cheng S, Honbo N, Piacentini L, Karliner JS, Lovett DH. A functional activating protein 1

(AP-1) site regulates matrix metalloproteinase 2 (MMP-2) transcription by cardiac cells through

interactions with JunB-Fra1 and JunB-FosB heterodimers. Biochem J. 2003;369(Pt 3):485–496.

Hezode C, Cazeneuve C, Coue O, Roudot-Thoraval F, Lonjon I, Bastie A, et al. Liver iron accumulation in

patients with chronic active hepatitis C: prevalence and role of hemochromatosis gene mutations and

relationship with hepatic histological lesions. J Hepatol. 1999;31(6):979–984.

Silva IS, Perez RM, Oliveira PV, Cantagalo MI, Dantas E, Sisti C, et al. Iron overload in patients with

JUNB SUPPRESSES HCV REPLICATION

18.

19.

20.

21.

22.

23.

24.

25.

26.

27.

28.

29.

30.

31.

32.

33.

chronic hepatitis C virus infection: clinical and histological study. J Gastroenterol Hepatol.

2005;20(2):243–248.

Tanaka H, Fujita N, Sugimoto R, Urawa N, Horiike S, Kobayashi Y, et al. Hepatic oxidative DNA damage

is associated with increased risk for hepatocellular carcinoma in chronic hepatitis C. Br J Cancer.

2008;98(3):580–586.

Schmidt PJ. Regulation of Iron Metabolism by Hepcidin under Conditions of Inflammation. J Biol Chem.

2015;290(31):18975–18983.

Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM, et al. Hepcidin regulates cellular

iron efflux by binding to ferroportin and inducing its internalization. Science. 2004;306(5704):2090–2093.

Kanamori Y, Murakami M, Matsui T, Funaba M. JNK facilitates IL-1beta-induced hepcidin transcription

via JunB activation. Cytokine. 2018;111:295–302.

Blight KJ, McKeating JA, Rice CM. Highly permissive cell lines for subgenomic and genomic hepatitis C

virus RNA replication. J Virol. 2002;76(24):13001–13014.

Lindenbach BD, Evans MJ, Syder AJ, Wolk B, Tellinghuisen TL, Liu CC, et al. Complete replication of

hepatitis C virus in cell culture. Science. 2005;309(5734):623–626.

Wakita T, Pietschmann T, Kato T, Date T, Miyamoto M, Zhao Z, et al. Production of infectious hepatitis C

virus in tissue culture from a cloned viral genome. Nat Med. 2005;11(7):791–796.

Murakami K, Ishii K, Ishihara Y, Yoshizaki S, Tanaka K, Gotoh Y, et al. Production of infectious hepatitis C

virus particles in three-dimensional cultures of the cell line carrying the genome-length dicistronic viral

RNA of genotype 1b. Virology. 2006;351(2):381–392.

Wozniak AL, Griffin S, Rowlands D, Harris M, Yi M, Lemon SM, et al. Intracellular proton conductance of

the hepatitis C virus p7 protein and its contribution to infectious virus production. PLoS Pathog.

2010;6(9):e1001087.

Meynard D, Babitt JL, Lin HY. The liver: conductor of systemic iron balance. Blood.

2014;123(2):168–176.

Muckenthaler MU, Rivella S, Hentze MW, Galy B. A Red Carpet for Iron Metabolism. Cell.

2017;168(3):344–361.

Foka P, Dimitriadis A, Karamichali E, Kyratzopoulou E, Giannimaras D, Koskinas J, et al. Alterations in

the iron homeostasis network: A driving force for macrophage-mediated hepatitis C virus persistency.

Virulence. 2016;7(6):679–690.

Sugimoto R, Fujita N, Tomosugi N, Hara N, Miyachi H, Tanaka H, et al. Impaired regulation of serum

hepcidin during phlebotomy in patients with chronic hepatitis C. Hepatol Res. 2009;39(6):619–624.

Liu H, Trinh TL, Dong H, Keith R, Nelson D, Liu C. Iron regulator hepcidin exhibits antiviral activity

against hepatitis C virus. PLoS One. 2012;7(10):e46631.

Fillebeen C, Rivas-Estilla AM, Bisaillon M, Ponka P, Muckenthaler M, Hentze MW, et al. Iron inactivates

the RNA polymerase NS5B and suppresses subgenomic replication of hepatitis C Virus. J Biol Chem.

2005;280(10):9049–9057.

Fillebeen C, Pantopoulos K. Iron inhibits replication of infectious hepatitis C virus in permissive Huh7.5.1

cells. J Hepatol. 2010;53(6):995–999.

E95

...

参考文献をもっと見る

全国の大学の
卒論・修論・学位論文

一発検索!

この論文の関連論文を見る