Volker Bruss 慕尼黑——HBV相关实验室及人物介绍系列
http://www.virologie.med.tu-muen ... chung-tum/ag-bruss/
Prof. Dr. Volker Bruss
Institute of Virology
TU Munich
Schneckenburgerstr. 8
81675 München
Germany
AG Bruss - Molecular biology of hepatitis B viruses
About 1/3 of the global human population is or has been infected with the hepatitis B virus (HBV) and 350 million people are persistent virus carriers being at risk to develop liver cirrhosis or liver cancer. An effective vaccine is available to prevent new infections. However, chronic infections and the resulting liver diseases are still serious medical problems and available therapies of limited efficacy. The development of new or the improvement of existing therapeutic concepts on a rational basis requires a deep knowledge of the biology of HBV on a molecular level.
Research topics
The work group “Molecular HBV Biology” studies several aspects of the viral life cycle:
(i) The virus particle is formed by the assembly of an icosahedral capsid containing the viral genome in the cytosol of the hepatocyte and subsequent envelopment of the capsid at an internal cellular membrane containing viral proteins. This envelopment or budding process translocates the capsid across the cellular membrane and allows the release of the infectious virus into the blood stream by the secretion machinery of the cell. A very specific interaction between the capsid surface and cytoplasmic domains of viral membrane proteins are required for and probably drive the envelopment process. We try to describe the molecular surfaces of capsid and envelope involved in budding. In addition we want to use this step as an antiviral target by developing small molecules specifically blocking capsid-envelope interactions.
(ii) During capsid formation a viral RNA molecule is packaged in the lumen together with a viral reverse transcriptase. This early, RNA containing, “immature” capsid is incompetent for budding. The reverse transcription of the RNA molecule in the capsid lumen generates the viral DNA genome. The capsid is then named “mature” and becomes competent for envelopment. We want to understand the molecular difference between immature and mature capsids and how this envelopment signal is generated.
(iii) After infection the viral DNA genome enters the nucleus and stays there as a covalently closed circular (ccc) molecule in an episomal state. Current therapies of HBV infections are not capable of directly reducing the amount of viral ccc DNA. Therefore, the virus often recurs after cessation of an antiviral therapy. We want to understand the steps leading from the open circular viral DNA genome in the capsid to the ccc DNA form of the genome in the nucleus and the cellular factors involved in this process.
A. Original publications
1. Ponsel D and Bruss V (2003) Mapping of amino acid side chains on the surface of hepatitis B virus capsids required for envelopment and virion formation. J Virol 77:416-422.
2. Kluge B, Schläger M, Pairan A, and Bruss V (2005) Determination of the minimal distance between the matrix and transmembrane domains of the large hepatitis B virus envelope protein. J Virol 79:7918-7921.
3. Schormann W, Kraft A, Ponsel D, and Bruss V (2006) Hepatitis B virus particle formation in the absence of pregenomic RNA and reverse transcriptase. J Virol 80:4187-4190.
4. Gudima S, He Y, Meier A, Chang J, Chen R, Jarnik M, Nicolas E, Bruss V, and Taylor J (2007) Assembly of hepatitis delta virus: particle characterization, including the ability to infect primary human hepatocytes. J Virol 81:3608-3617.
5. Gudima S, Meier A, Dunbrack R, Taylor J, and Bruss V (2007) Two potentially important elements of the hepatitis B virus large envelope protein are dispensable for the infectivity of hepatitis delta virus. J Virol 81:4343-44347.
B. Book Chapters
6. Gerlich WH, Bruss V, Heermann KH, Marquard O und Seifer M (1987) Presurface and precore products of human hepatitis B virus. In: Robinson W, Koike K und Will H (Herausgeber), “Hepadnaviruses”, UCLA Symposia on Molecular and Cellular Biology, New Series, Vol 70, p. 147-160. Alan R. Liss, Inc. New York.
7. Gerlich WH, Heermann KH, Bruss V, Höhne M, Krone B, Schaefer S und Seifer M (1988) Structure, expression and potential oncogenicity of hepatitis B virus proteins. In: Bannasch P und Keppler D (Herausgeber), “Liver Carcinoma”, p.139-163, Kluver, Dordrecht.
8. Melegari M, Bruss V und Gerlich WH (1991) The arginine-rich carboxy-terminal domain is necessary for RNA packaging by hepatitis B core protein. In Hollinger FB, Lemon SM und Margolis HS (Herausgeber), „Viral hepatitis and liver disease”, p. 164-168, Williams and Wilkins, Baltimore, USA.
9. Gerlich WH und Bruss V (1993) Functions of hepatitis B virus proteins and molecular targets for protective immunity. In: Ellis RW (Herausgeber), “Hepatitis B vaccines in clinical practice”, p. 41-82, Marcel Dekker, New York.
10. Bruss V (2004) Processing of hepatitis B virus surface proteins. Methods Mol Med 95:189-198.
C. Reviews
11. Bruss V (2007) Hepatitis B virus morphogenesis. World J Gastroenterol 13:65-73.
发表于 2009-10-8 19:59 Bigben
Volker Bruss，Helmholtz Zentrum München慕尼黑，德国
Blondot, M. L. and V. Bruss, et al. (2016). "Intracellular transport and egress of hepatitis B virus." J Hepatol 64(1 Suppl): S49-59.
Cui, X. and L. Luckenbaugh, et al. (2015). "Alteration of Mature Nucleocapsid and Enhancement of Covalently Closed Circular DNA Formation by Hepatitis B Virus Core Mutants Defective in Complete-Virion Formation." J Virol 89(19): 10064-72.
Orabi, A. and M. Bieringer, et al. (2015). "An aptamer against the matrix binding domain on the hepatitis B virus capsid impairs virion formation." J Virol.
Schittl, B. and V. Bruss (2014). "Mutational profiling of the variability of individual amino acid positions in the hepatitis B virus matrix domain." Virology 458-459: 183-9.
Siegler, V. D. and V. Bruss (2013). "Role of transmembrane domains of hepatitis B virus small surface proteins in subviral-particle biogenesis." J Virol 87(3): 1491-6.
Pairan, A. and V. Bruss (2009). "Functional surfaces of the hepatitis B virus capsid." J Virol 83(22): 11616-23.
Gudima, S. and Y. He, et al. (2008). "Primary human hepatocytes are susceptible to infection by hepatitis delta virus assembled with envelope proteins of woodchuck hepatitis virus." J Virol 82(15): 7276-83.
Gudima, S. and A. Meier, et al. (2007). "Two potentially important elements of the hepatitis B virus large envelope protein are dispensable for the infectivity of hepatitis delta virus." J Virol 81(8): 4343-7.
Gudima, S. and Y. He, et al. (2007). "Assembly of hepatitis delta virus: particle characterization, including the ability to infect primary human hepatocytes." J Virol 81(7): 3608-17.
Bruss, V. (2007). "Hepatitis B virus morphogenesis." World J Gastroenterol 13(1): 65-73.
Schormann, W. and A. Kraft, et al. (2006). "Hepatitis B virus particle formation in the absence of pregenomic RNA and reverse transcriptase." J Virol 80(8): 4187-90.
Kluge, B. and M. Schlager, et al. (2005). "Determination of the minimal distance between the matrix and transmembrane domains of the large hepatitis B virus envelope protein." J Virol 79(12): 7918-21.
Bruss, V. (2004). "Envelopment of the hepatitis B virus nucleocapsid." Virus Res 106(2): 199-209.
Bruss, V. (2004). "Processing of hepatitis B virus surface proteins." Methods Mol Med 95: 189-98.
Ponsel, D. and V. Bruss (2003). "Mapping of amino acid side chains on the surface of hepatitis B virus capsids required for envelopment and virion formation." J Virol 77(1): 416-22.
Hourioux, C. and J. Kneser, et al. (2002). "In vitro expression of human hepatitis B virus genomes carrying woodchuck hepatitis virus pre-S1 sequences." Intervirology 45(4-6): 233-6.
Bruss, V. (2002). "Revisiting the cytopathic effect of hepatitis B virus infection." Hepatology 36(6): 1327-9.
Koschel, M. and D. Oed, et al. (2000). "Hepatitis B virus core gene mutations which block nucleocapsid envelopment." J Virol 74(1): 1-7.
Geissler, M. and V. Bruss, et al. (1999). "Intracellular retention of hepatitis B virus surface proteins reduces interleukin-2 augmentation after genetic immunizations." J Virol 73(5): 4284-92.
Koschel, M. and R. Thomssen, et al. (1999). "Extensive mutagenesis of the hepatitis B virus core gene and mapping of mutations that allow capsid formation." J Virol 73(3): 2153-60.
Bruss, V. (1997). "A short linear sequence in the pre-S domain of the large hepatitis B virus envelope protein required for virion formation." J Virol 71(12): 9350-7.
Xu, Z. and V. Bruss, et al. (1997). "Formation of intracellular particles by hepatitis B virus large surface protein." J Virol 71(7): 5487-94.
Hildt, E. and G. Saher, et al. (1996). "The hepatitis B virus large surface protein (LHBs) is a transcriptional activator." Virology 225(1): 235-9.
Gerelsaikhan, T. and J. E. Tavis, et al. (1996). "Hepatitis B virus nucleocapsid envelopment does not occur without genomic DNA synthesis." J Virol 70(7): 4269-74.
Bruss, V. and J. Hagelstein, et al. (1996). "Myristylation of the large surface protein is required for hepatitis B virus in vitro infectivity." Virology 218(2): 396-9.
Bruss, V. and E. Gerhardt, et al. (1996). "Functions of the large hepatitis B virus surface protein in viral particle morphogenesis." Intervirology 39(1-2): 23-31.
Wounderlich, G. and V. Bruss (1996). "Characterization of early hepatitis B virus surface protein oligomers." Arch Virol 141(7): 1191-205.
Gerhardt, E. and V. Bruss (1995). "Phenotypic mixing of rodent but not avian hepadnavirus surface proteins into human hepatitis B virus particles." J Virol 69(2): 1201-8.
Bruss, V. and K. Vieluf (1995). "Functions of the internal pre-S domain of the large surface protein in hepatitisB virus particle morphogenesis." J Virol 69(11): 6652-7.
Bruss, V. and X. Lu, et al. (1994). "Post-translational alterations in transmembrane topology of the hepatitis B virus large envelope protein." EMBO J 13(10): 2273-9.
Bruss, V. and R. Thomssen (1994). "Mapping a region of the large envelope protein required for hepatitis B virion maturation." J Virol 68(3): 1643-50.
Bruss, V. and D. Ganem (1991). "Mutational analysis of hepatitis B surface antigen particle assembly and secretion." J Virol 65(7): 3813-20.
Macrae, D. R. and V. Bruss, et al. (1991). "Myristylation of a duck hepatitis B virus envelope protein is essential for infectivity but not for virus assembly." Virology 181(1): 359-63.
Bruss, V. and D. Ganem (1991). "The role of envelope proteins in hepatitis B virus assembly." Proc Natl Acad Sci U S A 88(3): 1059-63.
Bruss, V. and W. H. Gerlich (1988). "Formation of transmembraneous hepatitis B e-antigen by cotranslational in vitro processing of the viral precore protein." Virology 163(2): 268-75.
Uy, A. and V. Bruss, et al. (1986). "Precore sequence of hepatitis B virus inducing e antigen and membrane association of the viral core protein." Virology 155(1): 89-96.
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