HDAC11 restricts HBV replication through epigenetic repression of cccDNA transcription

Yuan, Ya-xiang; Zhao, Kaitao; Yao, Yongxuan; Liu, Canyu; Chen, Yingshan; Li, Jing; Wang, Yun; Pei, Rongjuan; Chen, Jizheng; Hu, Xue; Zhou, Yuan; Wu, Chunchen; Chen, Xinwen

doi:10.1016/j.antiviral.2019.104619

Cited by 34 publications

(23 citation statements)

References 35 publications

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“…Unfortunately, no crystal structure has been obtained for HDAC11. HDAC11 modulation has been shown to affect acetylation of several proteins, but catalytic dead HDAC11 mutants were not utilized in any of these studies so whether or not HDAC11 has any bona-fide deacetylation substrates remains unclear (Glozak and Seto, 2009;Wang et al, 2017;Gong et al, 2019;Yuan et al, 2019). HDAC11 is reported to interact with HDAC6 so it is possible that changes in acetylation following HDAC11 modulation occur indirectly through HDAC6 or with the help of some unidentified cofactor or interacting partner that is lost in purification of HDAC11 for in vitro assays (Gao et al, 2002).…”

Section: Hdac11mentioning

confidence: 99%

Lysine Fatty Acylation: Regulatory Enzymes, Research Tools, and Biological Function

Komaniecki

Lin

2021

Front. Cell Dev. Biol.

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Post-translational acylation of lysine side chains is a common mechanism of protein regulation. Modification by long-chain fatty acyl groups is an understudied form of lysine acylation that has gained increasing attention recently due to the characterization of enzymes that catalyze the addition and removal this modification. In this review we summarize what has been learned about lysine fatty acylation in the approximately 30 years since its initial discovery. We report on what is known about the enzymes that regulate lysine fatty acylation and their physiological functions, including tumorigenesis and bacterial pathogenesis. We also cover the effect of lysine fatty acylation on reported substrates. Generally, lysine fatty acylation increases the affinity of proteins for specific cellular membranes, but the physiological outcome depends greatly on the molecular context. Finally, we will go over the experimental tools that have been used to study lysine fatty acylation. While much has been learned about lysine fatty acylation since its initial discovery, the full scope of its biological function has yet to be realized.

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Section: Hdac11mentioning

confidence: 99%

Lysine Fatty Acylation: Regulatory Enzymes, Research Tools, and Biological Function

Komaniecki

Lin

2021

Front. Cell Dev. Biol.

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“…146,147 Meanwhile, HBx cellular transcripts can be produced due to the lack of a stop codon in the 3 0 end of the HBx ORF. 70,75,148,149 HBV DNA transcription and stability are further regulated by epigenetic effects, along with both viral and host factors. [150][151][152] Thus, integrated HBV DNA in the host genome may also recruit viral or host factors which perform epigenetic modifications, affecting either integrated HBV DNA expression or the host genome.…”

Section: Review Llmentioning

confidence: 99%

Insights into Hepatitis B Virus DNA Integration-55 Years after Virus Discovery

2020

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Hepatitis B virus (HBV), which was discovered in 1965, is a threat to global public health. HBV infects human hepatocytes and leads to acute and chronic liver diseases, and there is no cure. In cells infected by HBV, viral DNA can be integrated into the cellular genome. HBV DNA integration is a complicated process during the HBV life cycle. Although HBV integration normally results in replication-incompetent transcripts, it can still act as a template for viral protein expression. Of note, it is a primary driver of hepatocellular carcinoma (HCC). Recently, with the development of detection methods and research models, the molecular biology and the pathogenicity of HBV DNA integration have been better revealed. Here, we review the advances in the research of HBV DNA integration, including molecular mechanisms, detection methods, research models, the effects on host and viral gene expression, the role of HBV integrations in the pathogenesis of HCC, and potential treatment strategies. Finally, we discuss possible future research prospects of HBV DNA integration.

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“…HDACs play a pleiotropic role in cellular homeostasis with the different isoforms regulating unique cellular functions [18,21]. There have been multiple reports linking HDACs and HBV that were mainly focused on the histone deacetylation-dependent regulation of cccDNA accessibility to the transcriptional machinery [27][28][29][30][31][32]. However, comprehensive investigation of the effects of class I and II HDACs on HBV biosynthesis in hepatoma and nonhepatoma cells revealed that HDACs are not simply general repressors of HBV transcription (Fig 1).…”

Section: Plos Pathogensmentioning

confidence: 99%

“…Class I HDACs are generally regarded as the main deacetylases of histones among other roles in the cell, while class IIa and IIb HDACs are involved in a variety of cellular processes including cell cycle, DNA repair, differentiation, and apoptosis in deacetylase enzyme activity-dependent and -independent mechanisms [21][22][23][24][25][26]. There have been multiple reports linking HDACs to the accessibility of the transcriptional machinery to the HBV covalently closed circular DNA (cccDNA) present in cells as a nuclear chromatin template [27][28][29][30][31][32]. Interestingly, single-cell analysis of hepatocytes [33] revealed that the expression of HDAC5 correlates closely with the distinct zonal profile of viral biosynthesis [34] across the liver lobule in HBV transgenic mice (S1 Fig).…”

Section: Introductionmentioning

confidence: 99%

Modulation of hepatitis B virus pregenomic RNA stability and splicing by histone deacetylase 5 enhances viral biosynthesis

et al. 2020

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Hepatitis B virus (HBV) is a worldwide health problem without curative treatments. Investigation of the regulation of HBV biosynthesis by class I and II histone deacetylases (HDACs) demonstrated that catalytically active HDAC5 upregulates HBV biosynthesis. HDAC5 expression increased both the stability and splicing of the HBV 3.5 kb RNA without altering the translational efficiency of the viral pregenomic or spliced 2.2 kb RNAs. Together, these observations point to a broader role of HDAC5 in regulating RNA splicing and transcript stability while specifically identifying a potentially novel approach toward antiviral HBV therapeutic development.

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HDAC11 restricts HBV replication through epigenetic repression of cccDNA transcription

Cited by 34 publications

References 35 publications

Lysine Fatty Acylation: Regulatory Enzymes, Research Tools, and Biological Function

Lysine Fatty Acylation: Regulatory Enzymes, Research Tools, and Biological Function

Insights into Hepatitis B Virus DNA Integration-55 Years after Virus Discovery

Modulation of hepatitis B virus pregenomic RNA stability and splicing by histone deacetylase 5 enhances viral biosynthesis

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