Project Description

TP03A: A Dynamics of hepatitis B virus morphogenesis in persistent infection

In the serum of patients chronically infected with hepatitis B virus one does not only find complete DNA-containing virions, but also virions harbouring “empty” or RNA-containing capsids, respectively. The proportion of these non-canonical forms of virions varies drastically depending on the intrahepatic viral replication activity and the treatment status, and might be relevant for the continuous stimulation of the host immune response responsible for long-term liver inflammation ultimately resulting in cirrhosis and hepatocellular carcinoma.
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Seitz S, Urban S, Antoni C, Böttcher B. 2007. Cryo-electron microscopy of hepatitis B virions reveals variability in envelope capsid interactions. EMBO J. 26:4160-4167.
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Petersen J, Dandri M, Mier W, Lütgehetmann M, Volz T, von Weizsäcker F, Haberkorn U, Fischer L, Pollok JM, Erbes B, Seitz S, Urban S. 2008. Prevention of hepatitis B virus infection in vivo by entry inhibitors derived from the large envelope protein. Nat Biotechnol. 26:335-341.
Corcuera A, Stolle K, Hillmer S, Seitz S, Lee JY, Bartenschlager R, Birkmann A, Urban A. 2018. Novel non-heteroarylpyrimidine (HAP) capsid assembly modifiers have a different mode of action from HAPs in vitro. Antiviral Res. 158:135-142.
Schuetz AK, Hornemann, S, Wälti, MA, Greuter, L, Tiberi, C, Cadalbert, R, Ganter, M, Riek, R, Hammarström, P, Nilsson, KPR, Böckmann, A, Aguzzi, AA, Meier, BH. 2018. Binding of polythiophenes to amyloids: structural mapping of the pharmacophore. ACS Chem Neurosci. 9:475-481.
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Schütz, AK, Vagt, T, Huber, M, Ovchinnikova, OY, Cadalbert, R, Wall, J, Güntert, P, Böckmann, A, Glockshuber, R, Meier, BH. 2015. Atomic-resolution three-dimensional structure of amyloid β fibrils bearing the Osaka mutation. Angewandte Chemie. 54:331-335.
Herrmann, US, Schütz, AK, Shirani, H, Huang, D, Saban, D, Nuvolone, M, Li, B, Ballmer, B, Åslund, AK, Mason, JJ, Rushing, E, Budka, H, Nyström, S, Hammarström, P, Böckmann, A, Caflisch, A, Meier, BH, Nilsson, KP, Hornemann, S, Aguzzi, A. 2015. Structure-based drug design identifies polythiophenes as antiprion compounds. Science Translational Medicine. 7(299):ra123.