2. Academic Validation
  3. The MOV10 helicase restricts hepatitis B virus replication by inhibiting viral reverse transcription

The MOV10 helicase restricts hepatitis B virus replication by inhibiting viral reverse transcription

  • J Biol Chem. 2019 Dec 20;294(51):19804-19813. doi: 10.1074/jbc.RA119.009435.
Tingting Liu 1,  Qingsong Sun 2,  Yong Liu 3,  Shan Cen 4,  Quan Zhang 5 6
Affiliations

Affiliations

  • 1 Department of Transfusion Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008 China.
  • 2 Department of Emergency, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an 223301, China.
  • 3 Department of Laboratory Medicine, Nanjing Drum Tower Hospital and Jiangsu Key Laboratory for Molecular Medicine, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008 China.
  • 4 Institute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing 100050 China shancen@imb.pumc.edu.cn.
  • 5 Department of Laboratory Medicine, Nanjing Drum Tower Hospital and Jiangsu Key Laboratory for Molecular Medicine, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008 China huanlezq44@126.com.
  • 6 Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing Medical University, Nanjing 210008 China.
PMID: 31722967 DOI: 10.1074/jbc.RA119.009435
Abstract

Interferons inhibit viruses by inducing Antiviral protein expression. One of the interferon-induced Antiviral proteins, human Moloney leukemia virus 10 (MOV10), a superfamily 1 RNA helicase, has been shown to inhibit retroviruses and several RNA viruses. However, it remains undetermined whether MOV10 also inhibits DNA viruses, including hepatitis B virus (HBV). Here, we report that MOV10 dramatically reduces the levels of intracellular HBV DNA, resulting in significant inhibition of both the HBV experimental strain and the clinical isolates. Mechanistic experiments revealed that MOV10 interacts with HBV RNA and blocks the early step of viral reverse transcription, thereby impairing viral DNA synthesis, without affecting viral gene expression and pregenomic RNA encapsidation. Moreover, mutation of the helicase domain of MOV10 caused loss of binding to HBV RNA and of the anti-HBV activity. Together, our results indicate that MOV10 restricts HBV replication, insights that may open new avenues to the development of anti-HBV therapeutics.

Keywords

DNA viruses; Moloney leukemia virus 10 (MOV10); RNA helicase; RNA silencing; hepatitis B virus (HBV, Hep B); innate immunity; liver disease; viral replication; viral reverse transcription; virus-host interactions.

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