Kurzfassung

The hepatitis B virus (HBV) is an enveloped pararetrovirus that causes acute and chronic liver inflammation. Persistent HBV infections often result in fatal liver failure and globally rank among the most common infectious diseases. With the aim to improve knowledge of the biology of HBV infection, late steps of the viral replication cycle are studied in this project using cell culture models. The objective is focusing on HBV particle morphogenesis and its coordination by host factors. With...The hepatitis B virus (HBV) is an enveloped pararetrovirus that causes acute and chronic liver inflammation. Persistent HBV infections often result in fatal liver failure and globally rank among the most common infectious diseases. With the aim to improve knowledge of the biology of HBV infection, late steps of the viral replication cycle are studied in this project using cell culture models. The objective is focusing on HBV particle morphogenesis and its coordination by host factors. With regard to our current investigations, HBV produces not only complete infectious virions, but also non-enveloped capsids and empty envelope particles. The physiological relevance of the subviral particles is less understood; they could support viral transmission and viral immune evasion thereby facilitating the course of infection. Recent works show that HBV exploits different strategies and diverse host factors in order to form and release its three particle types. (1) Virions bud at intracellular membranes by the exploitation of cellular Rab GTPases, ubiquitin adaptors, ubiquitin ligases and specific proteins of the multivesicular endosome system (ESCRT). (2) Naked (nucleo)capsids are formed with the assistance of Rab33B and its autophagosomal Atg5/12/16L1 effector protein and are released in a non-lytic process using the cellular Alix protein. (3) Empty envelope particles mature in the secretory system and require the assistance of chaperones and probably Rab-mediated transport pathways. The participating cellular protein networks and their differential use by the virus are not fully resolved in their complexity, hierarchy and regulation and will be characterized integrative in continuing works using cell biological methods. Beside HBV-specific findings, we also expect to gain insights into intracellular membrane envelope reactions as well as into budding and reorganization processes at membranes. Moreover, improved knowledge of the underlying molecular mechanisms may help to define new targets for antiviral drugs.
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