301. Activities of endogenous APOBEC3s and uracil-DNA-glycosylase affect the hypermutation frequency of hepatitis B virus cccDNA.
- Author
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Kitamura K, Fukano K, Que L, Li Y, Wakae K, and Muramatsu M
- Subjects
- APOBEC Deaminases genetics, APOBEC Deaminases metabolism, DNA, Circular genetics, DNA, Circular metabolism, DNA, Viral genetics, DNA, Viral metabolism, Hepatitis B virus physiology, Humans, Uracil, Uracil-DNA Glycosidase genetics, Uracil-DNA Glycosidase metabolism, Virus Replication genetics, Hepatitis B, Hepatitis B Virus, Duck genetics, Hepatitis B Virus, Duck metabolism, Hepatitis B, Chronic
- Abstract
The covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) plays a key role in the persistence of viral infection. We have previously shown that overexpression of an antiviral factor APOBEC3G (A3G) induces hypermutation in duck HBV (DHBV) cccDNA, whereas uracil-DNA-glycosylase (UNG) reduces these mutations. In this study, using cell-culture systems, we examined whether endogenous A3s and UNG affect HBV cccDNA mutation frequency. IFNγ stimulation induced a significant increase in endogenous A3G expression and cccDNA hypermutation. UNG inhibition enhanced the IFNγ-mediated hypermutation frequency. Transfection of reconstructed cccDNA revealed that this enhanced hypermutation caused a reduction in viral replication. These results suggest that the balance of endogenous A3s and UNG activities affects HBV cccDNA mutation and replication competency.
- Published
- 2022
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