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Small animal model of hepatitis D virus infection

December 05, 2018

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Chronic delta hepatitis, caused by hepatitis delta virus (HDV), is now the most severe form of viral hepatitis and affects at least 20 million hepatitis B virus (HBV)-infected patients globally. HDV/HBV co- or superinfections are known to be major drivers for hepatocarcinogenesis. Development of an effective therapy against HDV has been impeded by a lack of suitable small-animal models. The authors generated a transgenic (tg) mouse model for HDV which expresses the functional receptor for HBV and HDV, the human sodium taurocholate co-transporting peptide NTCP. The authors found that both HBV and HDV enter hepatocytes in these mice in a glycoprotein-dependent manner, but one or more post-entry blocks then prevented HBV replication. However, HDV did persistently infect hNTCP tg mice co-expressing the HBV envelope, which is consistent with what is known about HDV dependency on HBsAg for packaging and spread. In immunocompromised mice lacking functional B, T and natural killer cells, the authors found that viraemia lasted at least 80 days, but then resolved within 14 days in immunocompetent animals, demonstrating that lymphocytes are critical for controlling HDV infection. While the acute HDV infection did not cause overt liver damage in the animal model, cell-intrinsic and cellular innate immune responses were found to be induced. The authors also found that single and dual treatment with myrcludex B and lonafarnib could efficiently suppress viraemia but doesn’t cure HDV infection at the doses tested. Therefore this small-animal model with inheritable susceptibility to HDV allows for more studies of the viral pathogenesis of HDV and for testing novel HDV therapies.

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Winer BY, Shirvani-Dastgerdi E, Bram Y, Sellau J, Low BE, et al. ISSN: Sci Transl Med; 10(447). pii: eaap9328

2018

Added: December 05, 2018