Analysis of additional glycosylatoin sites in the envelope protein of Hepatitis B Virus associated with HBV reactivation and hepatocellular carcinogenesis

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08479
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Aichi Medical University
• Principal Investigator: Kiyoaki Ito 愛知医科大学, 医学部, 教授 (50551420)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 糖鎖修飾変異

Outline of Final Research Achievements

There have been reported that "additional glycosylation" on the HBV envelope protein is frequently observed in cases of HBV reactivation and hepatocellular carcinogenesis. In this research project, we have investigated the frequency of occurrence of genomic mutations which create additional glycosylation site in envelope proteins in HBV reactivation cases using the next-generation sequencer (NGS) in Japan, and found that approximately 17% of HBV reactivation cases. We have introduced artificial genomic mutations that create additional glycosylation cite into HBV in vitro infectious model, and analyzed the effects of the artificial genomic mutations on HBV proliferation, viral protein expression, and immunogenicity to clarify the relationship with HBV reactivation and hepatocellular carcinogenesis.

Free Research Field

肝臓

Academic Significance and Societal Importance of the Research Achievements

HBVの再活性化はHBVキャリアや国民のおよそ20-25%にものぼるHBV既往感染者において免疫抑制や化学療法により発生する可能性があり、一度再活性化が発症すると重症化することが多くその対策は極めて重要である。また、HBVによる発癌はC型肝炎ウイルスによるものと比較して未だ制御には至っていない。本研究において、エンベロープ蛋白質追加糖鎖修飾変異のHBV再活性化症例における発現頻度を明らかにした。また、HBV in vitro感染モデルにおいてHBV再活性化や肝発癌に関連するメカニズムを明らかにした。本研究成果はHBV再活性化や発癌対策を講じるうえで極めて重要である。