2023 Fiscal Year Final Research Report
Mathematical modeling of HCV-based RNA virus mutation dynamics
| Project/Area Number |
22K15472
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 49060:Virology-related
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| Research Institution | Okayama University |
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Principal Investigator |
Ueda Youki 岡山大学, 医歯薬学域, 助教 (90756074)
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| Project Period (FY) |
2022-04-01 – 2024-03-31
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| Keywords | HCV / C型肝炎ウイルス / 数理化モデル / 長期継代 |
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| Outline of Final Research Achievements |
In hepatitis C virus (HCV), the accumulation of genetic mutations in the viral genome due to long-term infection and multiplication in the liver is considered to be the cause of drug-resistant mutations and hepatocarcinogenesis after healing. However, it is difficult to maintain HCV persistent infection systems over time, and studies of gene mutation accumulation have been rare because of frequent loss of structural regions and other events. In this study, an intracellular replication model of HCV was passively cultured for 13 years. The HCV genome was analyzed using a third-generation long-read sequencer to reveal the details of long-term mutation dynamics. A mathematical model was created from this data.
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| Free Research Field |
ウイルス
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| Academic Significance and Societal Importance of the Research Achievements |
本研究で用いたHCVレプリコン細胞株は申請者が所属する研究室において2002年と2003年に樹立したオリジナルの実験システムであり、HCVゲノムの進化ばかりでなく細胞がん化の要因を探る研究にも役立つと考え、HCVレプリコン細胞樹立時から継代を続けており、世界的にみてもHCVだけでなく他のウイルスでもこのような長期継代培養は皆無であり、今後もこのようなモデルの作成は極めて困難で、非常に貴重なモデルから得られた成果である。そして、この結果はHCVだけでな く他の新規ウイルスに対しても活用が大いに期待できる。
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