1887

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Volume 103, Issue 4

Activities of endogenous APOBEC3s and uracil-DNA-glycosylase affect the hypermutation frequency of hepatitis B virus cccDNA Open Access

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.

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  • Accepted:
  • Published Online:
Keyword(s): APOBEC , DNA repair , hepatitis B virus , host factor and mutation
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
© 2022 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
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2022-04-19
2024-04-19
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Activities of endogenous APOBEC3s and uracil-DNA-glycosylase affect the hypermutation frequency of hepatitis B virus cccDNA
J. Gen. Virol. 103, 001732 (2022); https://doi.org/10.1099/jgv.0.001732
/content/journal/jgv/10.1099/jgv.0.001732
/content/journal/jgv/10.1099/jgv.0.001732
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