A new HDV mouse model identifies mitochondrial antiviral signaling protein (MAVS) as a key player in IFN-β induction

Journal of Hepatology
Lester Suárez-AmaránGloria González-Aseguinolaza

Abstract

Studying hepatitis delta virus (HDV) and developing new treatments is hampered by the limited availability of small animal models. Herein, a description of a robust mouse model of HDV infection that mimics several important characteristics of the human disease is presented. HDV and hepatitis B virus (HBV) replication competent genomes were delivered to the mouse liver using adeno-associated viruses (AAV; AAV-HDV and AAV-HBV). Viral load, antigen expression and genomes were quantified at different time points after AAV injection. Furthermore, liver pathology, genome editing, and the activation of the innate immune response were evaluated. AAV-HDV infection initiated HDV replication in mouse hepatocytes. Genome editing was confirmed by the presence of small and large HDV antigens and sequencing. Viral replication was detected for 45days, even after the AAV-HDV vector had almost disappeared. In the presence of HBV, HDV infectious particles were detected in serum. Furthermore, as observed in patients, co-infection was associated with the reduction of HBV antigen expression and the onset of liver damage that included the alteration of genes involved in the development of liver pathologies. HDV replication induced a sustained type I ...Continue Reading

Citations

Apr 18, 2018·Cold Spring Harbor Perspectives in Medicine·Asuka Hirai-YukiStanley M Lemon
Jun 20, 2020·World Journal of Gastroenterology : WJG·Stephanie JungUlrike Protzer
Apr 16, 2019·World Journal of Gastroenterology : WJG·Cristina GodoyFrancisco Rodríguez-Frías
Nov 26, 2020·Viruses·Zhenfeng Zhang, Stephan Urban
Dec 11, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Estefania Rodriguez-GarciaMirja Hommel
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Oct 1, 2020·Liver International : Official Journal of the International Association for the Study of the Liver·Katja GierschMarc Lütgehetmann
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Apr 4, 2021·Viruses·Katja Giersch, Maura Dandri
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Dec 14, 2021·Cellular and Molecular Gastroenterology and Hepatology·Zaichao XuYuchen Xia

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