Visual Universitätsmedizin Mainz

Cell biology of hepatitis B and hepatitis D virus infections (Prange Laboratory)

Current Research


The Prange laboratory studies host/pathogen interactions with special focus on human hepatitis B and hepatitis D viruses. Human hepatitis B virus (HBV) is a global pathogen responsible for acute and chronic liver disease. Worldwide an estimated 250 million individuals are chronically infected and potentially develop liver cirrhosis and hepatocellular carcinoma. Persistent HBV infections are currently incurable. With the aim to improve knowledge of the biology of HBV infection and to seek for more effective antiviral strategies, we are studying HBV particle morphogenesis and its coordination by host cell factors. As the prototype member of the hepadnavirus family, HBV is an enveloped, DNA-containing pararetrovirus that replicates by reverse transcription. HBV produces not only complete infectious virions, but also non-enveloped capsids and empty envelope particles that are thought to support viral transmission and viral immune evasion, respectively. In order to form and release its particle types, HBV exploits different strategies and host factors. (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, termed ESCRTs. (2) Nucleocapsids are formed with the assistance of Rab33B and its autophagosomal Atg5-12/16L1 effector protein and non-enveloped capsids can be released in an uncommon, 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 GTPase-guided transport pathways. The participating cellular protein networks and mechanisms and their differential use by the virus are not fully resolved in their complexity, hierarchy and regulation and will be characterized in continuing works using a range of cell biological, biochemical, and imaging approaches. Future research activities will also focus on the hepatitis D virus (HDV), a unique viroid that requires the HBV envelope for propagation and infectivity.



Prof. Dr. rer. physiol. et med. habil. Prange
Prof. Dr. rer. physiol. et med. habil. Reinhild Prange
Function: Principal Investigator

06131 17-9344
06131 17-9021

Tatjana Döring
Function: Medical Technician

06131 17-9085
06131 17-9021

Lisa Zeyen
Function: Ph.D. Student



Döring T, Zeyen L, Bartusch C, Prange R. (2018). Hepatitis B virus subverts the autophagy elongation complex Atg5-12/16L1 and does not require Atg8/LC3 lipidation for viral maturation. J Virol, 92, e01513-17.

Bartusch C, Döring T, Prange R. (2017). Rab33B controls hepatitis B virus assembly by regulating core membrane association and nucleocapsid formation. Viruses, 9(6), doi:10.3390/v9060157.

Klionsky DJ, (...), Prange R, (...) (2016). Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy, 12, 1-222.

Bartusch C, Prange, R. (2016). ESCRT requirements for Murine Leukemia Virus release. Viruses, 8(4), doi:10.3390/v8040103.

Döring T, Prange, R. (2015). Rab33B and its autophagic Atg5/12/16L1 effector assist in hepatitis B virus naked capsid formation and release. Cell Microbiol, 17, 747- 64.

Stieler J, Prange R. (2014). Involvement of ESCRT-II in hepatitis B virus morphogenesis. PLOS ONE, 9, e91279.

Mades A, Gotthardt K, Awe K, Stieler J, Döring T, Füser S, Prange R. (2012). Role of human Sec63 in modulating the steady-state levels of multi-spanning membrane proteins. PLOS ONE, 7, e49243.

Prange, R. (2012). Host factors involved in hepatitis B virus maturation, assembly, and egress. Med Microbiol Immun, 201, 449-61.

Bardens A, Döring T, Stieler J, Prange R. (2011). Alix regulates egress of hepatitis B virus naked capsid particles in an ESCRT-independent manner. Cell Microbiol, 13, 602-19.

Döring T, Gotthardt K, Stieler J, Prange R. (2010). 2-Adaptin is functioning in the late endosomal sorting pathway and interacts with ESCRT-I and -III subunits. BBA-Mol Cell Res, 1803, 1252-64.

Awe A, Lambert C, Prange R. (2008). Mammalian BiP controls posttranslational ER translocation of the hepatitis B virus large envelope protein. FEBS LETT, 582, 3179-84.

Rost M, Döring T, Prange R. (2008). 2-Adaptin, a ubiquitin-interacting adaptor, is a substrate to coupled ubiquitination by the ubiquitin ligase Nedd4 and functions in the endosomal pathway. J Biol Chem, 83, 32119-30.

Funk A, Mhamdi M, Hohenberg H, Heeren J, Reimer R, Lambert C, Prange R, Sirma H. (2008). Duck Hepatitis B virus requires cholesterol for endosomal escape during virus entry. J Virol, 82, 10532-42.

Lambert C, Prange R. (2007). Posttranslational N-glycosylation of the hepatitis B virus large envelope protein. Virol J, 4, 45-53.

Lambert C, Döring T, Prange R. (2007). Hepatitis B virus maturation is sensitive to functional Inhibition of ESCRT-III, Vps4, and 2-Adaptin. J Virol, 81, 9050-60.

Rost M, Mann S, Lambert C, Döring T, Thomé N, Prange R. (2006). γ 2-Adaptin, a novel ubiquitin-interacting adaptor, and Nedd4 ubiquitin ligase control hepatitis B virus maturation. J Biol Chem, 281, 29297-308.

Lambert C, Thomé N, Kluck CJ, Prange R. (2004). Functional incorporation of green fluorescent protein into hepatitis B virus envelope particles. Virology, 330, 158-67.

Lambert C, Prange R. (2004). Development and characterization of a 293 cell line with regulatable expression of the hepatitis B virus large envelope protein. J Virol Methods, 121, 181-90.

Lambert C, Mann S, Prange R. (2004). Assessment of determinants affecting the dual topology of hepadnaviral large envelope proteins. J Gen Virol, 85, 1221-25.

Gerner P, Schäfer H, Prange R, Pravitt D, Wirth S. (2003). Functional analysis of a rare HBV deletion mutant in chronically infected children. Pediatr Res, 53, 891-97.

Lambert C, Prange R. (2003). Chaperone action in the posttranslational topological reorientation of the hepatitis B virus large envelope protein: implications for translocational regulation. Proc Natl Acad Sci USA, 100, 5199-204.

Lambert C, Prange R. (2001). Dual topology of the hepatitis B virus large envelope protein: determinants influencing posttranslational preS translocation. J Biol Chem, 276, 22265-72.

Hartmann-Stühler C, Prange R. (2001). Hepatitis B virus large envelope protein interacts with 2-adaptin, a clathrin adaptor-related protein. J Virol, 75, 5343-51.

Heinz D, Peters M, Prange R, Gerken G, Rose-John S. (2001). Possible role of human interleukin-6 and soluble interleukin-6 receptor in hepatitis B virus infection. J Viral Hepatitis, 8, 186-93.

Löffler-Mary H, Dumortier J, Klentsch-Zimmer C, Prange R. (2000). Hepatitis B virus assembly is sensitive to changes in the cytosolic S loop of the envelope proteins. Virology, 270, 358-67.

Prange R, Werr M, Löffler-Mary H. (1999). Chaperones involved in hepatitis B virus morphogenesis. Biol Chem, 380, 305-14.

Prange R, Werr M. (1999). DNA-mediated immunization of hepatitis B virus envelope proteins: preS antigen secretion enhances the humoral response. Vaccine, 17, 617-23.

Werr M, Prange R. (1998). Role for calnexin and N-glycosylation in the assembly and secretion of hepatitis B virus middle envelope protein particles. J Virol, 72, 778-82.

Löffler-Mary H, Werr M, Prange R. (1997). Sequence-specific repression of cotranslational translocation of the hepatitis B virus envelope proteins coincides with binding of heat shock protein Hsc70. Virology, 235, 144-52.

Prange R, Werr M, Birkner M, Hilfrich R, Streeck RE. (1995). Properties of modified hepatitis B surface antigen particles carrying preS epitopes. J Gen Virol, 76, 2131-40.

Prange R, Mangold CMT, Hilfrich R, Streeck RE. (1995). Mutational analysis of HBsAg assembly. Intervirology, 38, 16-23.

Prange R, Streeck RE. (1995). Novel transmembrane topology of the hepatitis B virus envelope proteins. EMBO J, 14, 247-56.

Prange R, Nagel R, Streeck RE. (1992). Deletions in the hepatitis B virus small envelope protein: effect on assembly and secretion of surface antigen particles. J Virol, 66, 5832-41.

Machein U, Nagel R, Prange R, Clemen A, Streeck RE. (1992). Deletion and insertion mutants of HBsAg particles. Arch Virol, 4, 133-36.

Prange R, Clemen A, Streeck RE. (1991). Myristylation is involved in intracellular retention of hepatitis B envelope proteins. J Virol, 65, 3919-23.


Deutsche Forschungsgemeinschaft (DFG)

Stipendien Stiftung Rheinland-Pfalz