An Immortalized Hepatocyte-Like Cell Line (imHC) Accommodated Complete Viral Lifecycle, Viral Persistence Form, cccDNA and Eventual Spreading of a Clinically-Isolated HBV
More than 350 million people worldwide have been persistently infected with the hepatitis B virus (HBV). Chronic HBV infection could advance toward liver cirrhosis and hepatocellular carcinoma. The intervention with prophylactic vaccine and conventional treatment could suppress HBV, but could not co...
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| Format: | Article |
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MDPI AG
2019-10-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/11/10/952 |
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| author | Khanit Sa-ngiamsuntorn Piyanoot Thongsri Yongyut Pewkliang Adisak Wongkajornsilp Pattida Kongsomboonchoke Phichaya Suthivanich Suparerk Borwornpinyo Suradej Hongeng |
| author_facet | Khanit Sa-ngiamsuntorn Piyanoot Thongsri Yongyut Pewkliang Adisak Wongkajornsilp Pattida Kongsomboonchoke Phichaya Suthivanich Suparerk Borwornpinyo Suradej Hongeng |
| author_sort | Khanit Sa-ngiamsuntorn |
| collection | DOAJ |
| description | More than 350 million people worldwide have been persistently infected with the hepatitis B virus (HBV). Chronic HBV infection could advance toward liver cirrhosis and hepatocellular carcinoma. The intervention with prophylactic vaccine and conventional treatment could suppress HBV, but could not completely eradicate it. The major obstacle for investigating curative antiviral drugs are the incompetence of hepatocyte models that should have closely imitated natural human infection. Here, we demonstrated that an immortalized hepatocyte-like cell line (imHC) could accommodate for over 30 days the entire life cycle of HBV prepared from either established cultured cells or clinically-derived fresh isolates. Normally, imHCs had intact interferon signaling with anti-viral action. Infected imHCs responded to treatments with direct-acting antiviral drugs (DAAs) and interferons (IFNs) by diminishing HBV DNA, the covalently closed circular DNA (cccDNA) surface antigen of HBV (HBsAg, aka the Australia antigen) and the hepatitis B viral protein (HBeAg). Notably, we could observe and quantify HBV spreading from infected cells to naïve cells using an imHC co-culture model. In summary, this study constructed a convenient HBV culture model that allows the screening for novel anti-HBV agents with versatile targets, either HBV entry, replication or cccDNA formation. Combinations of agents aiming at different targets should achieve a complete HBV eradication. |
| first_indexed | 2024-12-16T12:58:23Z |
| format | Article |
| id | doaj.art-e9b4eac815c9433c9badccb93eb29bea |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-12-16T12:58:23Z |
| publishDate | 2019-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-e9b4eac815c9433c9badccb93eb29bea2022-12-21T22:30:57ZengMDPI AGViruses1999-49152019-10-01111095210.3390/v11100952v11100952An Immortalized Hepatocyte-Like Cell Line (imHC) Accommodated Complete Viral Lifecycle, Viral Persistence Form, cccDNA and Eventual Spreading of a Clinically-Isolated HBVKhanit Sa-ngiamsuntorn0Piyanoot Thongsri1Yongyut Pewkliang2Adisak Wongkajornsilp3Pattida Kongsomboonchoke4Phichaya Suthivanich5Suparerk Borwornpinyo6Suradej Hongeng7Department of Biochemistry, Faculty of Pharmacy, Mahidol University, Bangkok 10400, ThailandDepartment of Biochemistry, Faculty of Pharmacy, Mahidol University, Bangkok 10400, ThailandExcellent Center for Drug Discovery, Faculty of Science, Mahidol University, Bangkok 10400, ThailandDepartment of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, ThailandDepartment of Biotechnology, Faculty of Science, Mahidol University, Bangkok 10400, ThailandExcellent Center for Drug Discovery, Faculty of Science, Mahidol University, Bangkok 10400, ThailandExcellent Center for Drug Discovery, Faculty of Science, Mahidol University, Bangkok 10400, ThailandDepartment of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, ThailandMore than 350 million people worldwide have been persistently infected with the hepatitis B virus (HBV). Chronic HBV infection could advance toward liver cirrhosis and hepatocellular carcinoma. The intervention with prophylactic vaccine and conventional treatment could suppress HBV, but could not completely eradicate it. The major obstacle for investigating curative antiviral drugs are the incompetence of hepatocyte models that should have closely imitated natural human infection. Here, we demonstrated that an immortalized hepatocyte-like cell line (imHC) could accommodate for over 30 days the entire life cycle of HBV prepared from either established cultured cells or clinically-derived fresh isolates. Normally, imHCs had intact interferon signaling with anti-viral action. Infected imHCs responded to treatments with direct-acting antiviral drugs (DAAs) and interferons (IFNs) by diminishing HBV DNA, the covalently closed circular DNA (cccDNA) surface antigen of HBV (HBsAg, aka the Australia antigen) and the hepatitis B viral protein (HBeAg). Notably, we could observe and quantify HBV spreading from infected cells to naïve cells using an imHC co-culture model. In summary, this study constructed a convenient HBV culture model that allows the screening for novel anti-HBV agents with versatile targets, either HBV entry, replication or cccDNA formation. Combinations of agents aiming at different targets should achieve a complete HBV eradication.https://www.mdpi.com/1999-4915/11/10/952hepatitis bviral spreadingcccdnahepatocytentcphbvcell culture |
| spellingShingle | Khanit Sa-ngiamsuntorn Piyanoot Thongsri Yongyut Pewkliang Adisak Wongkajornsilp Pattida Kongsomboonchoke Phichaya Suthivanich Suparerk Borwornpinyo Suradej Hongeng An Immortalized Hepatocyte-Like Cell Line (imHC) Accommodated Complete Viral Lifecycle, Viral Persistence Form, cccDNA and Eventual Spreading of a Clinically-Isolated HBV Viruses hepatitis b viral spreading cccdna hepatocyte ntcp hbv cell culture |
| title | An Immortalized Hepatocyte-Like Cell Line (imHC) Accommodated Complete Viral Lifecycle, Viral Persistence Form, cccDNA and Eventual Spreading of a Clinically-Isolated HBV |
| title_full | An Immortalized Hepatocyte-Like Cell Line (imHC) Accommodated Complete Viral Lifecycle, Viral Persistence Form, cccDNA and Eventual Spreading of a Clinically-Isolated HBV |
| title_fullStr | An Immortalized Hepatocyte-Like Cell Line (imHC) Accommodated Complete Viral Lifecycle, Viral Persistence Form, cccDNA and Eventual Spreading of a Clinically-Isolated HBV |
| title_full_unstemmed | An Immortalized Hepatocyte-Like Cell Line (imHC) Accommodated Complete Viral Lifecycle, Viral Persistence Form, cccDNA and Eventual Spreading of a Clinically-Isolated HBV |
| title_short | An Immortalized Hepatocyte-Like Cell Line (imHC) Accommodated Complete Viral Lifecycle, Viral Persistence Form, cccDNA and Eventual Spreading of a Clinically-Isolated HBV |
| title_sort | immortalized hepatocyte like cell line imhc accommodated complete viral lifecycle viral persistence form cccdna and eventual spreading of a clinically isolated hbv |
| topic | hepatitis b viral spreading cccdna hepatocyte ntcp hbv cell culture |
| url | https://www.mdpi.com/1999-4915/11/10/952 |
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