TGF-β triggers HBV cccDNA degradation through AID-dependent deamination.

Abstract:

:The covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) is a viral center molecule for HBV infection and persistence. However, the cellular restriction factors of HBV cccDNA are not well understood. Here, we show that TGF-β can induce nuclear viral cccDNA degradation and hypermutation via activation-induced cytidine deaminase (AID) deamination activity in hepatocytes. This suppression by TGF-β is abrogated when AID or the activity of uracil-DNA glycosylase (UNG) is absent, which indicates that AID deamination and the UNG-mediated excision of uracil act in concert to degrade viral cccDNA. Moreover, the HBV core protein promotes the interaction between AID and viral cccDNA. Overall, our results indicate a novel molecular mechanism that allows cytokine TGF-β to restrict viral nuclear cccDNA in innate immunity, thereby suggesting a novel method for potentially eliminating cccDNA.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Qiao Y,Han X,Guan G,Wu N,Sun J,Pak V,Liang G

doi

10.1002/1873-3468.12058

subject

Has Abstract

pub_date

2016-02-01 00:00:00

pages

419-27

issue

3

eissn

0014-5793

issn

1873-3468

journal_volume

590

pub_type

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