Journal
CELLS
Volume 10, Issue 11, Pages -Publisher
MDPI
DOI: 10.3390/cells10113019
Keywords
hepatoma cells; primary hepatocytes; liver; RNA virus; innate immunity; RIG-I; TLR3; interferon; arenavirus; coronavirus
Categories
Funding
- German Liver Foundation (Leberstiftung) [S163/10135/2017]
- German Research Foundation (DFG) [SFB900-C7, 158989968]
- Federal Ministry of Education and Research
- Ministry of Science and Culture of Lower Saxony through the Professorinnen Programm III
- Knut and Alice Wallenberg Foundation
- Hannover Biomedical Research School [SO-024]
- Helmholtz Association
- Swiss National Fonds [SINERGIA Nr. CRSII3_160780/1]
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Our study reveals that Hep3B cells closely mimic RNA sensing through RLR and TLR3 pathways in primary hepatocytes, indicating their potential as an in vitro model for studying immune response to RNA viruses in 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, 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.
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