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Short Communication

Inhibition of histone deacetylases stimulates HBV replication independent of protein X

    Maarten AA van de Klundert

    Department of Blood-borne Infections, Sanquin, Amsterdam, The Netherlands

    Department of Experimental Immunology, University of Amsterdam, Amsterdam, The Netherlands

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    ,
    Marjolein Swart

    Department of Experimental Immunology, University of Amsterdam, Amsterdam, The Netherlands

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    ,
    Hans L Zaaijer‡

    Department of Blood-borne Infections, Sanquin, Amsterdam, The Netherlands

    Laboratory of Clinical Virology of the Department of Medical Microbiology, Center for Infection & Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    ‡Authors contributed equally

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    &
    Neeltje A Kootstra‡

    *Author for correspondence:

    E-mail Address: n.a.kootstra@amc.uva.nl

    Department of Experimental Immunology, University of Amsterdam, Amsterdam, The Netherlands

    ‡Authors contributed equally

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    Published Online:27 Apr 2015https://doi.org/10.2217/fvl.15.22

    Abstract

    ABSTRACT 

    Aim: HBV expresses an accessory protein called X (HBx), which supports HBV replication by increasing transcription from episomal templates. Here, we investigate whether HBx augments HBV replication by interfering with the deacetylation of HBV DNA associated histones by histone deacetylases (HDACs). Materials & methods: To study the effect of HBx on episomal transcription, we transfected HEK 293 cells with luciferase-expressing constructs together with HBx in the presence and absence of HDAC inhibitors. We confirmed our results in the context of the full HBV replication cycle in HepG2 cells. Results & conclusion: Inhibition of HDAC activity and HBx expression stimulated transcription from episomal DNA independently, showing that HBx does not affect the histone deacetylation. HDAC inhibitors also augmented HBV replication in vitro independent of HBx expression. This suggests that treatment with HDAC inhibitors can (re)activate HBV infection in patients with cleared or ongoing HBV infection.

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