Project Description
Public­ations

TP15: Characterization of hepatitis D virus cell division-mediated spread and interference through innate and adaptive immune responses.

In addition to spread via assembled virions, HDV -in contrast to HBV- propagates through mitosis of hepatocytes, a spreading pathway inhibited upon activation of the interferon system. The aim of this project is the detailed understanding of cell division-mediated HDV spread, the response of surrounding immune cells, and its role in viral persistence, with the goal to define therapeutic targets to improve the therapy of chronic hepatitis D. We will investigate the multiple roles of the large HDV antigen for virus persistence, characterize interferon-stimulated genes that are involved in the regulation of HDV spread, and specify the role of the adaptive immune response in controlling HDV spread in patients.
Zhang Z, Filzmayer C, Ni Y, Sültmann H, Mutz P, Hiet M-S, Vondran FWR, Bartenschlager R, Urban S. (2018) Hepatitis D virus replication is sensed by MDA5 and induces IFN-β/λ responses in hepatocytes. J Hepatol. 69(1):25-35. doi: 10.1016/j.jhep.2018.02.021.
Gillich N*, Zhang Z*, Binder M, Urban S, Bartenschlager R. (2023) Effect of variants in LGP2 on MDA5-mediated activation of interferon response and suppression of hepatitis D virus replication. J Hepatol. 78(1):78-89. doi: 10.1016/j.jhep.2022.08.041.
Zhang Z, Ni Y, Lempp FA, Walter L, Mutz P, Bartenschlager R, Urban S. (2022) Hepatitis D virus-induced interferon response and administered interferons control cell division-mediated virus spread. J Hepatol. 77(4):957-966. doi: 10.1016/j.jhep.2022.05.023.
Urban S, Neumann-Haefelin C, Lampertico P. (2021) Hepatitis D virus in 2021: virology, immunology and new treatment approaches for a difficult-to-treat disease. Gut. 70(9):1782-1794. doi: 10.1136/gutjnl-2020-323888.
Nkongolo S, Mahamed D, Kuipery A, Sanchez Vasquez JD, Kim SC, Mehrotra A, Patel A, Hu C, McGilvray I, Feld J, Fung S, Chen D, Wallin J, Gaggar A, Janssen HLA*, Gehring AJ*. (2023) Longitudinal liver sampling in patients with chronic hepatitis B starting antiviral therapy reveals hepatotoxic CD8+ T cells. J Clin Invest. 133(1):e158903. doi: 10.1172/JCI158903.
Qu B*, Nebioglu F*, Leuthold MM, Ni Y, Mutz P, Beneke J, Erfle H, Vondran FWR, Bartenschlager R, Urban S. (2022) Dual role of neddylation in transcription of hepatitis B virus RNAs from cccDNA and production of viral surface antigen. JHEP Rep. 7;4(10):100551. doi: 10.1016/j.jhepr.2022.100551.
Kim SC, Wallin JJ, Ghosheh Y, Zahoor MA, Sanchez Vasquez JD, Nkongolo S, Fung S, Mendez P, Feld JJ, Janssen HLA, Gehring AJ. (2023) Efficacy of antiviral therapy and host-virus interactions visualised using serial liver sampling with fine-needle aspirates. JHEP Rep. 5(9):100817. doi: 10.1016/j.jhepr.2023.100817.
Zhang Z, Urban S. (2021) New insights into HDV persistence: The role of interferon response and implications for upcoming novel therapies. J Hepatol. 74(3):686-699. doi: 10.1016/j.jhep.2020.11.032.
Lempp FA, Roggenbach I, Nkongolo S, Sakin V, Schlund F, Schnitzler P, Wedemeyer H, Le Gal F, Gordien E, Yurdaydin C, Urban S. (2021) A Rapid Point-of-Care Test for the Serodiagnosis of Hepatitis Delta Virus Infection. Viruses. 13(12):2371. doi: 10.3390/v13122371.
Wedemeyer H, Schöneweis K, Bogomolov P, Blank A, Voronkova N, Stepanova T, Sagalova O, Chulanov V, Osipenko M, Morozov V, Gezvandova N, Sleptsova S, Bakulin IG, Khaertznova I, Rusanova M, Pathil A, Merle U, Bremer B, Allweis L, Lempp FA, Port K, Haag M, Schwab M, Schulze zur Wiesch J, Cornberg M, Haefeli WE, Dandri M, Alexandrov A, Urban S. (2023) Safety and efficacy of bulevirtide in combination with tenofovir disoproxil fumarate in patients with hepatitis B virus and hepatitis D virus coinfection (MYR202): a multicentre, randomised, parallelgroup, open-label, phase 2 trial. Lancet Infect Dis. 23(1):117-129. doi: 10.1016/S1473-3099(22)00318-8.