Characterization of RNA Sensing Pathways in Hepatoma Cell Lines and Primary Human Hepatocytes
The liver is targeted by several human pathogenic RNA viruses for viral replication and dissemination; despite this, the extent of innate immune sensing of RNA viruses by human hepatocytes is insufficiently understood to date. In particular, for highly human tropic viruses such as hepatitis C virus,...
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| Format: | Article |
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MDPI AG
2021-11-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/11/3019 |
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| author | Wiebke Nicolay Rebecca Moeller Sina Kahl Florian W. R. Vondran Thomas Pietschmann Stefan Kunz Gisa Gerold |
| author_facet | Wiebke Nicolay Rebecca Moeller Sina Kahl Florian W. R. Vondran Thomas Pietschmann Stefan Kunz Gisa Gerold |
| author_sort | Wiebke Nicolay |
| collection | DOAJ |
| description | The liver is targeted by several human pathogenic RNA viruses for viral replication and dissemination; despite this, the extent of innate immune sensing of RNA viruses by human hepatocytes is insufficiently understood to date. In particular, for highly human tropic viruses such as hepatitis C virus, cell culture models are needed to study immune sensing. However, several human hepatoma cell lines have impaired RNA sensing pathways and fail to mimic innate immune responses in the human liver. Here we compare the RNA sensing properties of six human hepatoma cell lines, namely Huh-6, Huh-7, HepG2, HepG2-HFL, Hep3B, and HepaRG, with primary human hepatocytes. We show that primary liver cells sense RNA through retinoic acid-inducible gene I (RIG-I) like receptor (RLR) and Toll-like receptor 3 (TLR3) pathways. Of the tested cell lines, Hep3B cells most closely mimicked the RLR and TLR3 mediated sensing in primary hepatocytes. This was shown by the expression of RLRs and TLR3 as well as the expression and release of bioactive interferon in primary hepatocytes and Hep3B cells. Our work shows that Hep3B cells partially mimic RNA sensing in primary hepatocytes and thus can serve as in vitro model to study innate immunity to RNA viruses in hepatocytes. |
| first_indexed | 2024-03-10T05:37:28Z |
| format | Article |
| id | doaj.art-8511463532ed436cb0a9439eac03877b |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T05:37:28Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-8511463532ed436cb0a9439eac03877b2023-11-22T22:50:08ZengMDPI AGCells2073-44092021-11-011011301910.3390/cells10113019Characterization of RNA Sensing Pathways in Hepatoma Cell Lines and Primary Human HepatocytesWiebke Nicolay0Rebecca Moeller1Sina Kahl2Florian W. R. Vondran3Thomas Pietschmann4Stefan Kunz5Gisa Gerold6TWINCORE—Centre for Experimental and Clinical Infection Research, Institute for Experimental Virology, 30625 Hannover, GermanyTWINCORE—Centre for Experimental and Clinical Infection Research, Institute for Experimental Virology, 30625 Hannover, GermanyTWINCORE—Centre for Experimental and Clinical Infection Research, Institute for Experimental Virology, 30625 Hannover, GermanyDepartment of General, Visceral and Transplant Surgery, Hannover Medical School, 30625 Hannover, GermanyTWINCORE—Centre for Experimental and Clinical Infection Research, Institute for Experimental Virology, 30625 Hannover, GermanyInstitute of Microbiology, Lausanne University Hospital, CH-1011 Lausanne, SwitzerlandTWINCORE—Centre for Experimental and Clinical Infection Research, Institute for Experimental Virology, 30625 Hannover, GermanyThe liver is targeted by several human pathogenic RNA viruses for viral replication and dissemination; despite this, the extent of innate immune sensing of RNA viruses by human hepatocytes is insufficiently understood to date. In particular, for highly human tropic viruses such as hepatitis C virus, cell culture models are needed to study immune sensing. However, several human hepatoma cell lines have impaired RNA sensing pathways and fail to mimic innate immune responses in the human liver. Here we compare the RNA sensing properties of six human hepatoma cell lines, namely Huh-6, Huh-7, HepG2, HepG2-HFL, Hep3B, and HepaRG, with primary human hepatocytes. We show that primary liver cells sense RNA through retinoic acid-inducible gene I (RIG-I) like receptor (RLR) and Toll-like receptor 3 (TLR3) pathways. Of the tested cell lines, Hep3B cells most closely mimicked the RLR and TLR3 mediated sensing in primary hepatocytes. This was shown by the expression of RLRs and TLR3 as well as the expression and release of bioactive interferon in primary hepatocytes and Hep3B cells. Our work shows that Hep3B cells partially mimic RNA sensing in primary hepatocytes and thus can serve as in vitro model to study innate immunity to RNA viruses in hepatocytes.https://www.mdpi.com/2073-4409/10/11/3019hepatoma cellsprimary hepatocytesliverRNA virusinnate immunityRIG-I |
| spellingShingle | Wiebke Nicolay Rebecca Moeller Sina Kahl Florian W. R. Vondran Thomas Pietschmann Stefan Kunz Gisa Gerold Characterization of RNA Sensing Pathways in Hepatoma Cell Lines and Primary Human Hepatocytes Cells hepatoma cells primary hepatocytes liver RNA virus innate immunity RIG-I |
| title | Characterization of RNA Sensing Pathways in Hepatoma Cell Lines and Primary Human Hepatocytes |
| title_full | Characterization of RNA Sensing Pathways in Hepatoma Cell Lines and Primary Human Hepatocytes |
| title_fullStr | Characterization of RNA Sensing Pathways in Hepatoma Cell Lines and Primary Human Hepatocytes |
| title_full_unstemmed | Characterization of RNA Sensing Pathways in Hepatoma Cell Lines and Primary Human Hepatocytes |
| title_short | Characterization of RNA Sensing Pathways in Hepatoma Cell Lines and Primary Human Hepatocytes |
| title_sort | characterization of rna sensing pathways in hepatoma cell lines and primary human hepatocytes |
| topic | hepatoma cells primary hepatocytes liver RNA virus innate immunity RIG-I |
| url | https://www.mdpi.com/2073-4409/10/11/3019 |
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