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Evaluation of HBsAg-associated hepatocarcinogenesis

Research Project

Project/Area Number 15K09033
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Gastroenterology
Research InstitutionNational Institute of Infectious Diseases

Principal Investigator

KATO TAKANOBU  国立感染症研究所, ウイルス第二部, 室長 (20333370)

Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsHBV / HBsAg / HCC / HBs抗原 / 細胞培養 / 肝発癌 / 粒子形成 / 細胞培養モデル / HBcr抗原 / B型肝炎ウイルス / B型肝炎 / プロモーター
Outline of Final Research Achievements

In this study, I evaluated the accumulation of HBsAg in hepatocytes by using the HBsAg expression vectors. I prepared the HBsAg expression vectors with several clones of genotypes A, B, and C. These vectors were transfected to HepG2 cells and intra- and extra-cellular HBsAg was measured. The expression of HBsAg of genotype C clones resulted in an intra-cellular accumulation of HBsAg in comparison with other genotypes. I also evaluated the effects of polymorphisms at the promoter region of HBsAg. I prepared the HBsAg expression vector harboring the amino acid polymorphisms in the promoter region of HBsAg. The amino acid substitution of T2768G was associated with the accumulation of HBsAg. These observations may explain the HBsAg-associated hepatocarcinogenesis.

Academic Significance and Societal Importance of the Research Achievements

我が国においてHBV感染はHCV感染に次ぐ主要な肝癌の原因であり、肝硬変を背景として発癌するケースが多い。しかし、HBVではHCVによる肝癌と異なり線維化の少ない慢性肝炎からの発癌も認めるため、発癌ポテンシャルはHCVより高いと考えられる。HBs抗原はウイルス粒子を構成する蛋白質であるが、その一方でL-HBs抗原を発現するトランスジェニックマウスでは肝障害とともに肝癌の発生が報告されている。またHBVのpreS領域に欠失を持つ患者では高率に肝癌を発症することも報告されている。本研究の成果はHBs抗原が関わる肝発癌機序の解明に繋がる知見と考えられる。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2020-03-30  

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