Investigation of pathophysiology in HBV infection using clinical samples

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K15941
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Osaka University
• Principal Investigator: Nakabori Tasuku 大阪大学, 医学部附属病院, 医員 (60795160)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: B型肝炎 / BCAT2

Outline of Final Research Achievements

RNA and DNA were extracted from the HBsAg-positive or -negative hepatocytes of 3 samples separately using laser capture microdissection and analyzed by real time PCR. Comprehensive analysis of gene expression levels using RNA-sequencing and paried-analysis were performed. Seven genes elevated more than twice in the HBsAg-positive hepatocytes (p<0.01). One of the seven was branched-chain amino acid transaminase 2 (BCAT2). In the PHHs, BCAT2 expression level elevated after HBV inoculation. Knockdown of BCAT2 significantly decreased pgRNA level in the HBV-infected PHHs. HBsAg and HBV DNA levels in the culture medium were significantly lower in the BCAT2 knockdown group.These results suggested that BCAT2 upregulation might contribute HBV replication.

Free Research Field

B型肝炎

Academic Significance and Societal Importance of the Research Achievements

B型肝炎は既存の治療薬ではウイルスを排除できず、新たな治療が必要である。しかし、B型肝炎ウイルス感染の病態生理は不明な点が多く、新規薬剤の開発は滞っている。本研究では分岐鎖アミノ酸(BCAA: branched-chain amino acid)代謝に関与するBCAA transaminase 2 (BCAT2)の発現上昇はB型肝炎ウイルス複製に寄与している可能性を示唆している。分岐鎖アミノ酸代謝は既存の抗ウイルス治療の標的にはなっていないため、新規治療標的になり得る可能性が期待される。