Role of hepatitis B core protein in HBV transcription and recruitment of histone acetyltransferases to cccDNA minichromosome
The hepatitis B core protein (HBc) has been suggested to interact with covalently closed circular DNA (cccDNA) and regulate hepatitis B virus (HBV) transcription. However, direct evidence is lacking. We aimed to identify the specific HBc region(s) responsible for transcription regulation and its int...
Gespeichert in:
| Veröffentlicht in: | Antiviral research 2017-08, Vol.144, p.1-7 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 7 |
|---|---|
| container_issue | |
| container_start_page | 1 |
| container_title | Antiviral research |
| container_volume | 144 |
| creator | Chong, Chun Kong Cheng, Ching Yan Serene Tsoi, Sin Yi Jasmine Huang, Fung-Yu Liu, Fen Seto, Wai-Kay Lai, Ching-Lung Yuen, Man-Fung Wong, Danny Ka-Ho |
| description | The hepatitis B core protein (HBc) has been suggested to interact with covalently closed circular DNA (cccDNA) and regulate hepatitis B virus (HBV) transcription. However, direct evidence is lacking. We aimed to identify the specific HBc region(s) responsible for transcription regulation and its interaction with cccDNA. Seventeen mutants with mutations at the four arginine-rich clusters of the HBc carboxyl-terminal domain (CTD) were created. The effect of HBc mutations on the levels of HBV DNA, RNA, and hepatitis B surface antigen (HBsAg) were measured. The association of cccDNA with mutant HBc and histone acetyltransferases (HATs) was assessed by chromatin immunoprecipitation (ChIP). Compared with wild-type HBc, HBc mutants with mutations in clusters III and IV resulted in a significant reduction in HBV RNA levels (all P |
| doi_str_mv | 10.1016/j.antiviral.2017.05.003 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1899117324</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0166354217300074</els_id><sourcerecordid>1899117324</sourcerecordid><originalsourceid>FETCH-LOGICAL-c371t-33256354b78aeccd7c473d1ca630f1cc6cb4602d1665175c23796402795fc1863</originalsourceid><addsrcrecordid>eNqFkE1r3DAQhkVpaDZp_0KrYy929WFL1nGTtE0gNBDSXoV2PCZabGkraQOB_vgq2TTXwsBcnneG9yHkE2ctZ1x92bYuFP_gk5tbwbhuWd8yJt-QFR-0aAwz6i1ZVVI1su_EMTnJecsYU9oM78ixGDpjBtWtyJ_bOCONE73HnSu--EzPKMSEdJdiQR9oncuzX7QkFzIkvys-BurCSBNC2vuyYCjPB3wuMSB1gOVxfsYnTC5jpiVSALj4saaLDx7uU1xijgu-J0eTmzN-eNmn5Oe3r3fnl831zfer8_V1A1Lz0kgpelVrbPTgEGDU0Gk5cnBKsokDKNh0iomxtu257kFIbVTHhDb9BHxQ8pR8PtytnX7vMRe7-Aw4zy5g3GfLB2M411J0FdUHFFLMOeFkd8kvLj1azuyTeru1r-rtk3rLelvV1-THlyf7zYLja-6f6wqsDwDWqg8ek83gMQCOvqosdoz-v0_-ArFNmv4</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1899117324</pqid></control><display><type>article</type><title>Role of hepatitis B core protein in HBV transcription and recruitment of histone acetyltransferases to cccDNA minichromosome</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Chong, Chun Kong ; Cheng, Ching Yan Serene ; Tsoi, Sin Yi Jasmine ; Huang, Fung-Yu ; Liu, Fen ; Seto, Wai-Kay ; Lai, Ching-Lung ; Yuen, Man-Fung ; Wong, Danny Ka-Ho</creator><creatorcontrib>Chong, Chun Kong ; Cheng, Ching Yan Serene ; Tsoi, Sin Yi Jasmine ; Huang, Fung-Yu ; Liu, Fen ; Seto, Wai-Kay ; Lai, Ching-Lung ; Yuen, Man-Fung ; Wong, Danny Ka-Ho</creatorcontrib><description><![CDATA[The hepatitis B core protein (HBc) has been suggested to interact with covalently closed circular DNA (cccDNA) and regulate hepatitis B virus (HBV) transcription. However, direct evidence is lacking. We aimed to identify the specific HBc region(s) responsible for transcription regulation and its interaction with cccDNA. Seventeen mutants with mutations at the four arginine-rich clusters of the HBc carboxyl-terminal domain (CTD) were created. The effect of HBc mutations on the levels of HBV DNA, RNA, and hepatitis B surface antigen (HBsAg) were measured. The association of cccDNA with mutant HBc and histone acetyltransferases (HATs) was assessed by chromatin immunoprecipitation (ChIP). Compared with wild-type HBc, HBc mutants with mutations in clusters III and IV resulted in a significant reduction in HBV RNA levels (all P < 0.05). HBc arginine clusters III and IV mutants also had a significantly lower levels of intracellular HBV DNA (<5% of wild-type; P < 0.001) and HBsAg (<10% of wild-type; P < 0.0001). cccDNA-ChIP assay demonstrated that HBc clusters III and IV mutants had a smaller degree of association with cccDNA (P < 0.001). In the HBc mutants, the association between HATs with cccDNA were reduced. In conclusion, HBc-CTD arginine residues at clusters III and IV play an important role in the regulation of HBV transcription as well as subsequent replication steps, likely through the reduced interaction of HBc with cccDNA and reduced acetylation of cccDNA-bound histones. These findings may provide clues to the identification of novel therapeutic targets against HBV.
•We assessed the role of hepatitis B core protein (HBc) in HBV transcription by mutational analysis.•HBV transcription levels in HBc mutants with mutations at arginine clusters III and IV were lower than wild-type HBc.•The interaction between HBc clusters III and IV mutants and covalently closed circular (ccc) DNA were reduced.•In strains with HBc clusters III and IV mutations, the recruitment of histone acetyltransferases to cccDNA is impeded.•HBc arginine clusters III and IV are potential therapeutic target sites against HBV replication.]]></description><identifier>ISSN: 0166-3542</identifier><identifier>EISSN: 1872-9096</identifier><identifier>DOI: 10.1016/j.antiviral.2017.05.003</identifier><identifier>PMID: 28499864</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Chromatin Immunoprecipitation ; Covalently closed circular DNA ; DNA Mutational Analysis ; DNA, Circular - metabolism ; DNA, Viral - metabolism ; HBV transcription ; Hep G2 Cells ; Hepatitis B Core Antigens - genetics ; Hepatitis B Core Antigens - metabolism ; Hepatitis B core protein ; Hepatitis B virus ; Hepatitis B virus - genetics ; Histone acetylation ; Histone Acetyltransferases - metabolism ; Humans ; Protein Binding ; RNA, Viral - metabolism ; Transcription, Genetic</subject><ispartof>Antiviral research, 2017-08, Vol.144, p.1-7</ispartof><rights>2017 Elsevier B.V.</rights><rights>Copyright © 2017 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c371t-33256354b78aeccd7c473d1ca630f1cc6cb4602d1665175c23796402795fc1863</citedby><cites>FETCH-LOGICAL-c371t-33256354b78aeccd7c473d1ca630f1cc6cb4602d1665175c23796402795fc1863</cites><orcidid>0000-0001-9078-5005</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0166354217300074$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28499864$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chong, Chun Kong</creatorcontrib><creatorcontrib>Cheng, Ching Yan Serene</creatorcontrib><creatorcontrib>Tsoi, Sin Yi Jasmine</creatorcontrib><creatorcontrib>Huang, Fung-Yu</creatorcontrib><creatorcontrib>Liu, Fen</creatorcontrib><creatorcontrib>Seto, Wai-Kay</creatorcontrib><creatorcontrib>Lai, Ching-Lung</creatorcontrib><creatorcontrib>Yuen, Man-Fung</creatorcontrib><creatorcontrib>Wong, Danny Ka-Ho</creatorcontrib><title>Role of hepatitis B core protein in HBV transcription and recruitment of histone acetyltransferases to cccDNA minichromosome</title><title>Antiviral research</title><addtitle>Antiviral Res</addtitle><description><![CDATA[The hepatitis B core protein (HBc) has been suggested to interact with covalently closed circular DNA (cccDNA) and regulate hepatitis B virus (HBV) transcription. However, direct evidence is lacking. We aimed to identify the specific HBc region(s) responsible for transcription regulation and its interaction with cccDNA. Seventeen mutants with mutations at the four arginine-rich clusters of the HBc carboxyl-terminal domain (CTD) were created. The effect of HBc mutations on the levels of HBV DNA, RNA, and hepatitis B surface antigen (HBsAg) were measured. The association of cccDNA with mutant HBc and histone acetyltransferases (HATs) was assessed by chromatin immunoprecipitation (ChIP). Compared with wild-type HBc, HBc mutants with mutations in clusters III and IV resulted in a significant reduction in HBV RNA levels (all P < 0.05). HBc arginine clusters III and IV mutants also had a significantly lower levels of intracellular HBV DNA (<5% of wild-type; P < 0.001) and HBsAg (<10% of wild-type; P < 0.0001). cccDNA-ChIP assay demonstrated that HBc clusters III and IV mutants had a smaller degree of association with cccDNA (P < 0.001). In the HBc mutants, the association between HATs with cccDNA were reduced. In conclusion, HBc-CTD arginine residues at clusters III and IV play an important role in the regulation of HBV transcription as well as subsequent replication steps, likely through the reduced interaction of HBc with cccDNA and reduced acetylation of cccDNA-bound histones. These findings may provide clues to the identification of novel therapeutic targets against HBV.
•We assessed the role of hepatitis B core protein (HBc) in HBV transcription by mutational analysis.•HBV transcription levels in HBc mutants with mutations at arginine clusters III and IV were lower than wild-type HBc.•The interaction between HBc clusters III and IV mutants and covalently closed circular (ccc) DNA were reduced.•In strains with HBc clusters III and IV mutations, the recruitment of histone acetyltransferases to cccDNA is impeded.•HBc arginine clusters III and IV are potential therapeutic target sites against HBV replication.]]></description><subject>Chromatin Immunoprecipitation</subject><subject>Covalently closed circular DNA</subject><subject>DNA Mutational Analysis</subject><subject>DNA, Circular - metabolism</subject><subject>DNA, Viral - metabolism</subject><subject>HBV transcription</subject><subject>Hep G2 Cells</subject><subject>Hepatitis B Core Antigens - genetics</subject><subject>Hepatitis B Core Antigens - metabolism</subject><subject>Hepatitis B core protein</subject><subject>Hepatitis B virus</subject><subject>Hepatitis B virus - genetics</subject><subject>Histone acetylation</subject><subject>Histone Acetyltransferases - metabolism</subject><subject>Humans</subject><subject>Protein Binding</subject><subject>RNA, Viral - metabolism</subject><subject>Transcription, Genetic</subject><issn>0166-3542</issn><issn>1872-9096</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1r3DAQhkVpaDZp_0KrYy929WFL1nGTtE0gNBDSXoV2PCZabGkraQOB_vgq2TTXwsBcnneG9yHkE2ctZ1x92bYuFP_gk5tbwbhuWd8yJt-QFR-0aAwz6i1ZVVI1su_EMTnJecsYU9oM78ixGDpjBtWtyJ_bOCONE73HnSu--EzPKMSEdJdiQR9oncuzX7QkFzIkvys-BurCSBNC2vuyYCjPB3wuMSB1gOVxfsYnTC5jpiVSALj4saaLDx7uU1xijgu-J0eTmzN-eNmn5Oe3r3fnl831zfer8_V1A1Lz0kgpelVrbPTgEGDU0Gk5cnBKsokDKNh0iomxtu257kFIbVTHhDb9BHxQ8pR8PtytnX7vMRe7-Aw4zy5g3GfLB2M411J0FdUHFFLMOeFkd8kvLj1azuyTeru1r-rtk3rLelvV1-THlyf7zYLja-6f6wqsDwDWqg8ek83gMQCOvqosdoz-v0_-ArFNmv4</recordid><startdate>201708</startdate><enddate>201708</enddate><creator>Chong, Chun Kong</creator><creator>Cheng, Ching Yan Serene</creator><creator>Tsoi, Sin Yi Jasmine</creator><creator>Huang, Fung-Yu</creator><creator>Liu, Fen</creator><creator>Seto, Wai-Kay</creator><creator>Lai, Ching-Lung</creator><creator>Yuen, Man-Fung</creator><creator>Wong, Danny Ka-Ho</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-9078-5005</orcidid></search><sort><creationdate>201708</creationdate><title>Role of hepatitis B core protein in HBV transcription and recruitment of histone acetyltransferases to cccDNA minichromosome</title><author>Chong, Chun Kong ; Cheng, Ching Yan Serene ; Tsoi, Sin Yi Jasmine ; Huang, Fung-Yu ; Liu, Fen ; Seto, Wai-Kay ; Lai, Ching-Lung ; Yuen, Man-Fung ; Wong, Danny Ka-Ho</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c371t-33256354b78aeccd7c473d1ca630f1cc6cb4602d1665175c23796402795fc1863</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Chromatin Immunoprecipitation</topic><topic>Covalently closed circular DNA</topic><topic>DNA Mutational Analysis</topic><topic>DNA, Circular - metabolism</topic><topic>DNA, Viral - metabolism</topic><topic>HBV transcription</topic><topic>Hep G2 Cells</topic><topic>Hepatitis B Core Antigens - genetics</topic><topic>Hepatitis B Core Antigens - metabolism</topic><topic>Hepatitis B core protein</topic><topic>Hepatitis B virus</topic><topic>Hepatitis B virus - genetics</topic><topic>Histone acetylation</topic><topic>Histone Acetyltransferases - metabolism</topic><topic>Humans</topic><topic>Protein Binding</topic><topic>RNA, Viral - metabolism</topic><topic>Transcription, Genetic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chong, Chun Kong</creatorcontrib><creatorcontrib>Cheng, Ching Yan Serene</creatorcontrib><creatorcontrib>Tsoi, Sin Yi Jasmine</creatorcontrib><creatorcontrib>Huang, Fung-Yu</creatorcontrib><creatorcontrib>Liu, Fen</creatorcontrib><creatorcontrib>Seto, Wai-Kay</creatorcontrib><creatorcontrib>Lai, Ching-Lung</creatorcontrib><creatorcontrib>Yuen, Man-Fung</creatorcontrib><creatorcontrib>Wong, Danny Ka-Ho</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Antiviral research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chong, Chun Kong</au><au>Cheng, Ching Yan Serene</au><au>Tsoi, Sin Yi Jasmine</au><au>Huang, Fung-Yu</au><au>Liu, Fen</au><au>Seto, Wai-Kay</au><au>Lai, Ching-Lung</au><au>Yuen, Man-Fung</au><au>Wong, Danny Ka-Ho</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Role of hepatitis B core protein in HBV transcription and recruitment of histone acetyltransferases to cccDNA minichromosome</atitle><jtitle>Antiviral research</jtitle><addtitle>Antiviral Res</addtitle><date>2017-08</date><risdate>2017</risdate><volume>144</volume><spage>1</spage><epage>7</epage><pages>1-7</pages><issn>0166-3542</issn><eissn>1872-9096</eissn><abstract><![CDATA[The hepatitis B core protein (HBc) has been suggested to interact with covalently closed circular DNA (cccDNA) and regulate hepatitis B virus (HBV) transcription. However, direct evidence is lacking. We aimed to identify the specific HBc region(s) responsible for transcription regulation and its interaction with cccDNA. Seventeen mutants with mutations at the four arginine-rich clusters of the HBc carboxyl-terminal domain (CTD) were created. The effect of HBc mutations on the levels of HBV DNA, RNA, and hepatitis B surface antigen (HBsAg) were measured. The association of cccDNA with mutant HBc and histone acetyltransferases (HATs) was assessed by chromatin immunoprecipitation (ChIP). Compared with wild-type HBc, HBc mutants with mutations in clusters III and IV resulted in a significant reduction in HBV RNA levels (all P < 0.05). HBc arginine clusters III and IV mutants also had a significantly lower levels of intracellular HBV DNA (<5% of wild-type; P < 0.001) and HBsAg (<10% of wild-type; P < 0.0001). cccDNA-ChIP assay demonstrated that HBc clusters III and IV mutants had a smaller degree of association with cccDNA (P < 0.001). In the HBc mutants, the association between HATs with cccDNA were reduced. In conclusion, HBc-CTD arginine residues at clusters III and IV play an important role in the regulation of HBV transcription as well as subsequent replication steps, likely through the reduced interaction of HBc with cccDNA and reduced acetylation of cccDNA-bound histones. These findings may provide clues to the identification of novel therapeutic targets against HBV.
•We assessed the role of hepatitis B core protein (HBc) in HBV transcription by mutational analysis.•HBV transcription levels in HBc mutants with mutations at arginine clusters III and IV were lower than wild-type HBc.•The interaction between HBc clusters III and IV mutants and covalently closed circular (ccc) DNA were reduced.•In strains with HBc clusters III and IV mutations, the recruitment of histone acetyltransferases to cccDNA is impeded.•HBc arginine clusters III and IV are potential therapeutic target sites against HBV replication.]]></abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>28499864</pmid><doi>10.1016/j.antiviral.2017.05.003</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0001-9078-5005</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0166-3542 |
| ispartof | Antiviral research, 2017-08, Vol.144, p.1-7 |
| issn | 0166-3542 1872-9096 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1899117324 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Chromatin Immunoprecipitation Covalently closed circular DNA DNA Mutational Analysis DNA, Circular - metabolism DNA, Viral - metabolism HBV transcription Hep G2 Cells Hepatitis B Core Antigens - genetics Hepatitis B Core Antigens - metabolism Hepatitis B core protein Hepatitis B virus Hepatitis B virus - genetics Histone acetylation Histone Acetyltransferases - metabolism Humans Protein Binding RNA, Viral - metabolism Transcription, Genetic |
| title | Role of hepatitis B core protein in HBV transcription and recruitment of histone acetyltransferases to cccDNA minichromosome |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-25T16%3A17%3A23IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Role%20of%20hepatitis%20B%20core%20protein%20in%20HBV%20transcription%20and%20recruitment%20of%20histone%20acetyltransferases%20to%20cccDNA%20minichromosome&rft.jtitle=Antiviral%20research&rft.au=Chong,%20Chun%20Kong&rft.date=2017-08&rft.volume=144&rft.spage=1&rft.epage=7&rft.pages=1-7&rft.issn=0166-3542&rft.eissn=1872-9096&rft_id=info:doi/10.1016/j.antiviral.2017.05.003&rft_dat=%3Cproquest_cross%3E1899117324%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1899117324&rft_id=info:pmid/28499864&rft_els_id=S0166354217300074&rfr_iscdi=true |