2016 Fiscal Year Final Research Report
Host factors involved in HBV cccDNA maintenance
Project/Area Number |
26460993
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Gastroenterology
|
Research Institution | Kanazawa University |
Principal Investigator |
|
Project Period (FY) |
2014-04-01 – 2017-03-31
|
Keywords | B型肝炎ウイルス |
Outline of Final Research Achievements |
Covalently closed circular DNA (cccDNA) forms a template for the replication of hepatitis B virus (HBV). Despite the crucial role of cccDNA in viral persistence, little is known about the host factors that target this viral intermediate. Recent studies have revealed that AID/APOBEC3 cytidine deaminase family members can induce C-to-U hypermutation on viral genome and restrict viral replication. Uracil residues in DNA are removed by base excision repair (BER) enzyme, uracil DNA glycosylase (UNG), when cytidine deamination is occurred in host genome. We investigated whether uracil residues were generated in HBV cccDNA by APOBEC3G and removed by UNG using in vitro. We found that IFNγ stimulation of hepatocyte cell lines induced the endogenous APOBEC3G expression and HBV cccDNA hypermutation. When UNG activity was inhibited, the IFNγ-mediated hypermutation of cccDNA was enhanced. Our result indicate that BER pathway cancels the mutations of the cccDNA generated by APOBEC proteins.
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Free Research Field |
ウイルス学
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