Project Description

TP23: Dynamics of hepatitis B virus morphogenesis and its alterations during chronic infection

In the serum of patients with chronic hepatitis B one does not only find complete DNA-containing virions, but also virions harbouring “empty” or RNA-containing capsids. The proportion of these forms in chronic carriers varies drastically depending on the intrahepatic viral replication activity and the treatment status. We therefore propose that HBV particles are subject to defined ultrastructural dynamics with a series of thermodynamically driven, temporally and spatially regulated events during particle morphogenesis. This might be key to determining the fate of nucleocapsids in the host cell by deciding between either secretion as enveloped virions or recycling to the nucleus to sustain the pool of viral covalently closed circular DNA, which is the central reservoir for HBV persistence.
A. Schütz AK, Hornemann, S, Wälti, MA, Greuter, L, Tiberi, C, Cadalbert, R, Ganter, M, Riek, R, Hammar-ström, P, Nilsson, KPR, Böckmann, A, Aguzzi, AA, Meier, BH. 2018. Binding of polythiophenes to amy-loids: structural mapping of the pharmacophore. ACS Chem Neurosci. 9(3):475-481.
B. Lauber C, Seitz S, Mattei S, Suh A, Beck J, Herstein J, Börold J, Salzburger W, Kaderali L, Briggs J, Bartenschlager R. 2017. Deciphering the origin and evolution of hepatitis B viruses by means of a fami-ly of nonenveloped fish viruses. Cell Host Microbe. 22(3):387-399.e6.
C. Schuetz, AK, Kay, LE 2016. A dynamic molecular basis for malfunction in disease mutants of p97/VCP. eLife. 5:e20143.
D. Seitz S, Iancu C, Volz T, Mier W, Dandri M, Urban S, Bartenschlager R. 2016. A slow maturation pro-cess renders hepatitis B virus infectious. Cell Host Microbe. 20(1):25-35.
E. 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. Angew Chem Int Ed Engl. 54(1):331-335.
F. 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. Sci Transl Med. 7(299):ra123.
G. Petersen J, Dandri M, Mier W, Lütgehetmann M, Volz T, von Weizsäcker F, Haberkorn U, Fischer L, Pol-lok JM, Erbes B, Seitz S, Urban S. 2008. Prevention of hepatitis B virus infection in vivo by entry inhibi-tors derived from the large envelope protein. Nat Biotechnol. 26(3):335-341.
H. 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(18):4160-4167.