1887

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.

Funding
This study was supported by the:
  • Takeda Science Foundation
    • Principle Award Recipient: KouichiKitamura
  • Japan Agency for Medical Research and Development (Award JP19fk0210053)
    • Principle Award Recipient: MasamichiMuramatsu
  • Japan Agency for Medical Research and Development (Award JP18fk0310103)
    • Principle Award Recipient: MasamichiMuramatsu
  • Japan Agency for Medical Research and Development (Award JP18fk0310119)
    • Principle Award Recipient: KouichiKitamura
  • Japan Society for the Promotion of Science (Award 19K07583)
    • Principle Award Recipient: MasamichiMuramatsu
  • Japan Society for the Promotion of Science (Award 20K08380)
    • Principle Award Recipient: KouichiKitamura
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
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2022-04-19
2022-05-18
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