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HBV RNA virion-like particles produced under nucleos(t)ide analogues treatment are mainly replication-deficient

  • Jie Wang
    Affiliations
    State Key Laboratory of Natural and Biomimetic Drugs, Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
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  • Qiuju Sheng
    Affiliations
    Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, China
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  • Yang Ding
    Affiliations
    Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, China
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  • Ran Chen
    Affiliations
    State Key Laboratory of Natural and Biomimetic Drugs, Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
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  • Xiaofeng Sun
    Affiliations
    State Key Laboratory of Natural and Biomimetic Drugs, Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
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  • Xiangmei Chen
    Affiliations
    State Key Laboratory of Natural and Biomimetic Drugs, Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
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  • Xiaoguang Dou
    Correspondence
    Corresponding authors. Addresses: State Key Laboratory of Natural and Biomimetic Drugs, Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, China. Tel.: +86 10 82805136; fax: +86 10 82805136 (F. Lu), or Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, China (X. Dou).
    Affiliations
    Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, China
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  • Fengmin Lu
    Correspondence
    Corresponding authors. Addresses: State Key Laboratory of Natural and Biomimetic Drugs, Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, China. Tel.: +86 10 82805136; fax: +86 10 82805136 (F. Lu), or Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, China (X. Dou).
    Affiliations
    State Key Laboratory of Natural and Biomimetic Drugs, Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
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Published:November 04, 2017DOI:https://doi.org/10.1016/j.jhep.2017.10.030
      With great interest, we read the manuscript “Relationship between serum HBV RNA levels and intrahepatic viral as well as histologic activity markers in entecavir-treated patients” by Wang et al. published in Journal of Hepatology.
      • Wang J.
      • Yu Y.
      • Li G.
      • Shen C.
      • Meng Z.
      • Zheng J.
      • et al.
      Relationship between serum HBV-RNA levels and intrahepatic viral as well as histologic activity markers in entecavir-treated patients.
      The authors revealed that serum hepatitis B virus (HBV) RNA levels reflected intrahepatic transcriptional activity of covalently closed circular DNA (cccDNA) and were associated with liver histopathology in patients receiving entecavir (ETV) therapy. Moreover, quasispecies analysis found that serum HBV RNA resembled intrahepatic viral RNA but not cccDNA, implying that the nascent variants of HBV RNA detected in liver biopsy samples were not present in cccDNA under nucleos(t)ide analogues (NAs) treatment. In addition, the authors proposed that the viral forms in the reservoir of HBV RNA virion-like particles might be composed of viral transcriptional products from static (persistent present) active cccDNA and newly produced viral progeny from de novo infections. Since serum HBV DNA was undetectable in these ETV-treated patients, we postulated that the presence of HBV RNA virion-like particles might contribute to the de novo infections. Based on the fact that the cells transfected with pregenomic RNA (pgRNA) of a DNA virus can produce complete infectious viruses,
      • Huang M.J.
      • Summers J.
      Infection initiated by the RNA pregenome of a DNA virus.
      the infection potential of HBV RNA virion-like particles containing HBV pgRNA has been previously proposed.
      • Jansen L.
      • Kootstra N.A.
      • van Dort K.A.
      • Takkenberg R.B.
      • Reesink H.W.
      • Zaaijer H.L.
      Hepatitis B virus pregenomic RNA is present in virions in plasma and is associated with a response to pegylated interferon alfa-2a and nucleos(t)ide analogues.
      • Wang J.
      • Shen T.
      • Huang X.
      • Kumar G.R.
      • Chen X.
      • Zeng Z.
      • et al.
      Serum hepatitis B virus is encapsidated pregenome RNA that may be associated with persistence of viral infection and rebound.

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      Author names in bold designate shared co-first authorship

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