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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Autores principales:	Wiebke Nicolay, Rebecca Moeller, Sina Kahl, Florian W. R. Vondran, Thomas Pietschmann, Stefan Kunz, Gisa Gerold
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	hepatoma cells primary hepatocytes liver RNA virus innate immunity RIG-I Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/8511463532ed436cb0a9439eac03877b
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spelling	oai:doaj.org-article:8511463532ed436cb0a9439eac03877b2021-11-25T17:10:29ZCharacterization of RNA Sensing Pathways in Hepatoma Cell Lines and Primary Human Hepatocytes10.3390/cells101130192073-4409https://doaj.org/article/8511463532ed436cb0a9439eac03877b2021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3019https://doaj.org/toc/2073-4409The 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.Wiebke NicolayRebecca MoellerSina KahlFlorian W. R. VondranThomas PietschmannStefan KunzGisa GeroldMDPI AGarticlehepatoma cellsprimary hepatocytesliverRNA virusinnate immunityRIG-IBiology (General)QH301-705.5ENCells, Vol 10, Iss 3019, p 3019 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hepatoma cells primary hepatocytes liver RNA virus innate immunity RIG-I Biology (General) QH301-705.5
spellingShingle	hepatoma cells primary hepatocytes liver RNA virus innate immunity RIG-I Biology (General) QH301-705.5 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
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.
format	article
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
title	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_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_sort	characterization of rna sensing pathways in hepatoma cell lines and primary human hepatocytes
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/8511463532ed436cb0a9439eac03877b
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Characterization of RNA Sensing Pathways in Hepatoma Cell Lines and Primary Human Hepatocytes

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