Adenosine deaminase acting on RNA-1 (ADAR1) inhibits hepatitis B virus (HBV) replication by enhancing microRNA-122 processing

The Journal of Biological Chemistry
Guangyan LiuLinghua Li

Abstract

Adenosine deaminases acting on RNA-1 (ADAR1) involves adenosine to inosine RNA editing and microRNA processing. ADAR1 is known to be involved in the replication of various viruses, including hepatitis C and D. However, the role of ADAR1 in hepatitis B virus (HBV) infection has not yet been elucidated. Here, for the first time, we demonstrated ADAR1 antiviral activity against HBV. ADAR1 has two splicing isoforms in human hepatocytes: constitutive p110 protein and interferon-α (IFN-α)-responsive p150 protein. We found that overexpression of ADAR1 decreased HBV RNA in an HBV culture model. A catalytic-site mutant ADAR1 also decreased HBV RNA levels, whereas another adenosine deaminases that act on the RNA (ADAR) family protein, ADAR2, did not. Moreover, the induction of ADAR1 by stimulation with IFN-α also reduced HBV RNA levels. Decreases in endogenous ADAR1 expression by knock-down or knock-out increased HBV RNA levels. A major hepatocyte-specific microRNA, miRNA-122, was found to be positively correlated with ADAR1 expression, and exogenous miRNA-122 decreased both HBV RNA and DNA, whereas, conversely, transfection with a miRNA-122 inhibitor increased them. The reduction of HBV RNA by ADAR1 expression was abrogated by p53 knock...Continue Reading

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Citations

Oct 24, 2019·International Journal of Molecular Sciences·Po-Shuan HuangKwang-Huei Lin
Dec 15, 2019·International Journal of Molecular Sciences·Marta Correia de SousaMichelangelo Foti
Feb 23, 2021·Frontiers in Immunology·Armando Andres Roca SuarezJoachim Lupberger
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Jul 19, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·YueJiao WangNing Zhang
Apr 22, 2021·Annual Review of Virology·Christian K PfallerCharles E Samuel

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