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Dual role of neddylation in transcription of hepatitis B virus RNAs from cccDNA and production of viral surface antigen

HBV persistence is maintained by both an episomal covalently closed circular (ccc)DNA reservoir and genomic integration of HBV DNA fragments. While cccDNA transcription is regulated by Cullin4A-DDB1-HBx-mediated degradation of the SMC5/6 complex, HBsAg expression from integrants is largely SMC5/6 in...

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Main Authors: Qu, Bingqian (Author) , Nebioglu, Firat (Author) , Leuthold, Mila (Author) , Ni, Yi (Author) , Mutz, Pascal (Author) , Beneke, Jürgen (Author) , Erfle, Holger (Author) , Vondran, Florian W. R. (Author) , Bartenschlager, Ralf (Author) , Urban, Stephan (Author)
Format: Article (Journal)
Language:English
Published: 7 August 2022
In: JHEP reports
Year: 2022, Volume: 4, Issue: 10, Pages: 1-13
ISSN:2589-5559
DOI:10.1016/j.jhepr.2022.100551
Online Access:Resolving-System, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.jhepr.2022.100551
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S2589555922001239
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Author Notes:Bingqian Qu, Firat Nebioglu, Mila M. Leuthold, Yi Ni, Pascal Mutz, Jürgen Beneke, Holger Erfle, Florian W.R. Vondran, Ralf Bartenschlager, Stephan Urban
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Summary:HBV persistence is maintained by both an episomal covalently closed circular (ccc)DNA reservoir and genomic integration of HBV DNA fragments. While cccDNA transcription is regulated by Cullin4A-DDB1-HBx-mediated degradation of the SMC5/6 complex, HBsAg expression from integrants is largely SMC5/6 independent. Inhibiting neddylation of Cullin-RING ubiquitin ligases impairs degradation of substrates. Herein, we show that targeting neddylation pathway components by small-interfering (si)RNAs or the drug MLN4924 (pevonedistat) suppresses expression of HBV proteins from both cccDNA and integrants.
Item Description:Gesehen am 06.12.2022
Physical Description:Online Resource
ISSN:2589-5559
DOI:10.1016/j.jhepr.2022.100551

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