Elucidation of synergy in hepatocarcinogenesis by hepatitis B virus, inflammation and hypernutrition

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H04807
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: The University of Tokyo
• Principal Investigator: KOIKE KAZUHIKO 東京大学, 医学部附属病院, 教授 (80240703)
• Co-Investigator(Kenkyū-buntansha): 森屋 恭爾 東京大学, 医学部附属病院, 教授 (00272550) ; 堤 武也 東京大学, 医科学研究所, 准教授 (00726739)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 肝癌 / B型肝炎 / 炎症 / ウイルス / 肥満

Outline of Final Research Achievements

Hepatitis B virus (HBV) infection can lead to cirrhosis and hepatocellular carcinoma. Episomal viral covalently closed circular DNA (cccDNA) minichromosomes and transcripts from cccDNA continue to be expressed over the long term. We showed that the host protein DExH-box helicase 9 (DXH9) is associated with viral RNAs. We also showed that viral-derived circular RNA is produced during HBV replication, and the amount is increased by knockdown of the DHX9 protein, which, in turn, results in decreased viral protein levels but does not affect the levels of HBV DNA. In addition, through a comprehensive compound screen using a newly constructed split luciferase system, we showed that nitazoxanide (NTZ) efficiently inhibits the HBx-DDB1 interaction. NTZ significantly restores Smc5 protein levels and suppresses viral transcription and viral protein production in the HBV minicircle system, in in vitro HBV replicating models, and in human primary hepatocytes naturally infected with HBV.

Free Research Field

内科学