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  1. Article ; Online: Characterization of RNA Sensing Pathways in Hepatoma Cell Lines and Primary Human Hepatocytes

    Wiebke Nicolay / Rebecca Moeller / Sina Kahl / Florian W. R. Vondran / Thomas Pietschmann / Stefan Kunz / Gisa Gerold

    Cells, Vol 10, Iss 3019, p

    2021  Volume 3019

    Abstract: 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 ... ...

    Abstract 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.
    Keywords hepatoma cells ; primary hepatocytes ; liver ; RNA virus ; innate immunity ; RIG-I ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2021-11-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Fluvastatin mitigates SARS-CoV-2 infection in human lung cells

    Francisco J. Zapatero-Belinchón / Rebecca Moeller / Lisa Lasswitz / Marco van Ham / Miriam Becker / Graham Brogden / Ebba Rosendal / Wenjie Bi / Belén Carriquí-Madroñal / Koushikul Islam / Annasara Lenman / Antonia P. Gunesch / Jared Kirui / Thomas Pietschmann / Anna K. Överby / Lothar Jänsch / Gisa Gerold

    iScience, Vol 24, Iss 12, Pp 103469- (2021)

    2021  

    Abstract: Summary: Clinical data of patients suffering from COVID-19 indicates that statin therapy, used to treat hypercholesterolemia, is associated with a better disease outcome. Whether statins directly affect virus replication or influence the clinical outcome ...

    Abstract Summary: Clinical data of patients suffering from COVID-19 indicates that statin therapy, used to treat hypercholesterolemia, is associated with a better disease outcome. Whether statins directly affect virus replication or influence the clinical outcome through modulation of immune responses is unknown. We therefore investigated the effect of statins on SARS-CoV-2 infection in human lung cells and found that only fluvastatin inhibited low and high pathogenic coronaviruses in vitro and ex vivo in a dose-dependent manner. Quantitative proteomics revealed that fluvastatin and other tested statins modulated the cholesterol synthesis pathway without altering innate antiviral immune responses in infected lung epithelial cells. However, fluvastatin treatment specifically downregulated proteins that modulate protein translation and viral replication. Collectively, these results support the notion that statin therapy poses no additional risk to individuals exposed to SARS-CoV-2 and that fluvastatin has a moderate beneficial effect on SARS-CoV-2 infection of human lung cells.
    Keywords Drugs ; Virology ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2021-12-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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