Elucidation of the characteristics of genetic changes in hepatitis B and C viruses and their relationship with clinical conditions

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07980
• 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: Kobe University
• Principal Investigator: Ueda Yoshihide 神戸大学, 医学研究科, 特命教授 (90378662)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: C型肝炎ウイルス / B型肝炎ウイルス / 遺伝子変異

Outline of Final Research Achievements

We identified HCV genome sequences in the serum of patients with chronic hepatitis C and recurrent hepatitis C after liver transplantation before and after anti-HCV treatment, using a single-molecule real-time sequencer and next-generation sequencer. We conducted a molecular phylogenetic tree analysis of changes in HCV gene sequences and found that transition mutations occur frequently as a characteristic of HCV gene mutation bias, and that A→G and U→C mutations are particularly frequent. On the other hand, known drug resistance mutations were also caused by transversion mutations.
As a result of similar analysis of the HBV gene sequences of chronic hepatitis B patients, structural changes in HBV including deletions in the HBV preS/S region and C region were found in many cases, and the relationship with clinical course was clarified.

Free Research Field

肝臓病学

Academic Significance and Societal Importance of the Research Achievements

本研究では、C型ならびにB型肝炎ウイルスの感染患者体内で生じている遺伝子変異バイアスを明らかにし、遺伝子構造変化も含めた遺伝子変化と病態との関連を解明した。これらの遺伝子配列の変化が臨床経過と関連していることから、臨床像の予測や個々の症例に最適な治療法の検討へと繋がることが期待できる。また、近年問題となった新型コロナウイルス感染症（COVID-19）のように、社会的に問題となり早急な対策が必要となる新規ウイルス感染症の遺伝子変異の解析にも応用できる解析手法を確立したため、様々なウイルスの遺伝子変化と病態との関係を解明する研究法として今後の学術的な発展が期待できる。