Characterization of a Cell Culture System of Persistent Hepatitis E Virus Infection in the Human HepaRG Hepatic Cell Line
Hepatitis E virus (HEV) is considered as an emerging global health problem. In most cases, hepatitis E is a self-limiting disease and the virus is cleared spontaneously without the need of antiviral therapy. However, immunocompromised individuals can develop chronic infection and liver fibrosis that...
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| Language: | English |
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MDPI AG
2021-03-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/13/3/406 |
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| author | Marie Pellerin Edouard Hirchaud Yannick Blanchard Nicole Pavio Virginie Doceul |
| author_facet | Marie Pellerin Edouard Hirchaud Yannick Blanchard Nicole Pavio Virginie Doceul |
| author_sort | Marie Pellerin |
| collection | DOAJ |
| description | Hepatitis E virus (HEV) is considered as an emerging global health problem. In most cases, hepatitis E is a self-limiting disease and the virus is cleared spontaneously without the need of antiviral therapy. However, immunocompromised individuals can develop chronic infection and liver fibrosis that can progress rapidly to cirrhosis and liver failure. The lack of efficient and relevant cell culture system and animal models has limited our understanding of the biology of HEV and the development of effective drugs for chronic cases. In the present study, we developed a model of persistent HEV infection in human hepatocytes in which HEV replicates efficiently. This HEV cell culture system is based on differentiated HepaRG cells infected with an isolate of HEV-3 derived from a patient suffering from acute hepatitis E. Efficient replication was maintained for several weeks to several months as well as after seven successive passages on HepaRG naïve cells. Moreover, after six passages onto HepaRG, we found that the virus was still infectious after oral inoculation into pigs. We also showed that ribavirin had an inhibitory effect on HEV replication in HepaRG. In conclusion, this system represents a relevant and efficient in vitro model of HEV replication that could be useful to study HEV biology and identify effective antiviral drugs against chronic HEV infection. |
| first_indexed | 2024-03-09T05:31:14Z |
| format | Article |
| id | doaj.art-58c511f3834149fbb705fc48414e9bc4 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T05:31:14Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-58c511f3834149fbb705fc48414e9bc42023-12-03T12:32:35ZengMDPI AGViruses1999-49152021-03-0113340610.3390/v13030406Characterization of a Cell Culture System of Persistent Hepatitis E Virus Infection in the Human HepaRG Hepatic Cell LineMarie Pellerin0Edouard Hirchaud1Yannick Blanchard2Nicole Pavio3Virginie Doceul4UMR 1161 Virologie, INRAE, ANSES, Ecole Nationale Vétérinaire d’Alfort, Université Paris-Est, 94700 Maisons-Alfort, FranceAgence Nationale de Sécurité Sanitaire, De L’environnement et du Travail (ANSES), Laboratory of Ploufragan-Plouzané-Niort, Viral Genetic and Biosafety (GVB) Unit, 22440 Ploufragan, FranceAgence Nationale de Sécurité Sanitaire, De L’environnement et du Travail (ANSES), Laboratory of Ploufragan-Plouzané-Niort, Viral Genetic and Biosafety (GVB) Unit, 22440 Ploufragan, FranceUMR 1161 Virologie, INRAE, ANSES, Ecole Nationale Vétérinaire d’Alfort, Université Paris-Est, 94700 Maisons-Alfort, FranceUMR 1161 Virologie, INRAE, ANSES, Ecole Nationale Vétérinaire d’Alfort, Université Paris-Est, 94700 Maisons-Alfort, FranceHepatitis E virus (HEV) is considered as an emerging global health problem. In most cases, hepatitis E is a self-limiting disease and the virus is cleared spontaneously without the need of antiviral therapy. However, immunocompromised individuals can develop chronic infection and liver fibrosis that can progress rapidly to cirrhosis and liver failure. The lack of efficient and relevant cell culture system and animal models has limited our understanding of the biology of HEV and the development of effective drugs for chronic cases. In the present study, we developed a model of persistent HEV infection in human hepatocytes in which HEV replicates efficiently. This HEV cell culture system is based on differentiated HepaRG cells infected with an isolate of HEV-3 derived from a patient suffering from acute hepatitis E. Efficient replication was maintained for several weeks to several months as well as after seven successive passages on HepaRG naïve cells. Moreover, after six passages onto HepaRG, we found that the virus was still infectious after oral inoculation into pigs. We also showed that ribavirin had an inhibitory effect on HEV replication in HepaRG. In conclusion, this system represents a relevant and efficient in vitro model of HEV replication that could be useful to study HEV biology and identify effective antiviral drugs against chronic HEV infection.https://www.mdpi.com/1999-4915/13/3/406hepatitis E viruscell culture modelpersistent infection |
| spellingShingle | Marie Pellerin Edouard Hirchaud Yannick Blanchard Nicole Pavio Virginie Doceul Characterization of a Cell Culture System of Persistent Hepatitis E Virus Infection in the Human HepaRG Hepatic Cell Line Viruses hepatitis E virus cell culture model persistent infection |
| title | Characterization of a Cell Culture System of Persistent Hepatitis E Virus Infection in the Human HepaRG Hepatic Cell Line |
| title_full | Characterization of a Cell Culture System of Persistent Hepatitis E Virus Infection in the Human HepaRG Hepatic Cell Line |
| title_fullStr | Characterization of a Cell Culture System of Persistent Hepatitis E Virus Infection in the Human HepaRG Hepatic Cell Line |
| title_full_unstemmed | Characterization of a Cell Culture System of Persistent Hepatitis E Virus Infection in the Human HepaRG Hepatic Cell Line |
| title_short | Characterization of a Cell Culture System of Persistent Hepatitis E Virus Infection in the Human HepaRG Hepatic Cell Line |
| title_sort | characterization of a cell culture system of persistent hepatitis e virus infection in the human heparg hepatic cell line |
| topic | hepatitis E virus cell culture model persistent infection |
| url | https://www.mdpi.com/1999-4915/13/3/406 |
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