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2. HBV shows different levels of adaptation to HLA class I-associated selection pressure correlating with markers of replication

Author

Schwarz, Tatjana, Ptok, Johannes, Damagnez, Maximilian, Menne, Christopher, Alizei, Elahe Salimi, Lang-Meli, Julia, Maas, Michelle, Habermann, Daniel, Hoffmann, Daniel, Schulze zur Wiesch, Julian, Lauer, Georg M., Kefalakes, Helenie, Cornberg, Markus, Kraft, Anke R.M., Gliga, Smaranda, Bock, Hans H., Horn, Peter A., Maini, Mala K., Thimme, Robert, Wedemeyer, Heiner, Nattermann, Jacob, Heinemann, Falko M., Luedde, Tom, Neumann-Haefelin, Christoph, Walker, Andreas, and Timm, Jörg

Published
2024
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3. Nervensystem Nervensystem

Author

May, Petra, Becker, Cord-Michael, Bock, Hans H., Heinrich, Peter C., editor, Müller, Matthias, editor, Graeve, Lutz, editor, and Koch, Hans-Georg, editor

Published
2022
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6. Proof of infectivity of hepatitis E virus particles from the ejaculate of chronically infected patients.

Author

Schemmerer, Mathias, Bock, Hans H., Schattenberg, Jörn M., Huber, Samuel, Polywka, Susanne, Mader, Maria, Lohse, Ansgar W., Todt, Daniel, Steinmann, Eike, Wenzel, Jürgen J., Horvatits, Thomas, and Pischke, Sven

Subjects
HEPATITIS E virus, VIRAL load, VIRAL shedding, CELL culture, SEXUAL partners
Abstract

Recently, hepatitis E virus (HEV, Paslahepevirus balayani) particles were detected for the first time in the ejaculate of two chronically infected patients. Since then, we have been able to detect HEV in ejaculate in five further patients, and thus in a total of seven out of nine (78%) chronically infected men (age 36–67 years, median 56 years). In five patients, the HEV RNA concentration was more than 100‐fold higher compared to the serum, while in two patients, the viral load was more than 10‐fold lower. However, it has remained unclear whether viral particles shed in the ejaculate were infectious, as a previous cell culture model had failed to demonstrate the infectivity. In the current study, we employed an optimized HEV cell culture system based on overconfluent PLC/PRF/5 cells to investigate the infectivity of HEV particles from ejaculate and other body fluids. With this approach, we were able to show for the first time that HEV particles in the ejaculate from several patients were infectious. HEV replicated to high viral loads of 1e9 HEV RNA copies per ml. This indicates that HEV‐positive ejaculate could bear a risk of infection for sexual partners. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Nervensystem

Author

May, Petra, Becker, Cord-Michael, Bock, Hans H., Heinrich, Peter C., editor, Müller, Matthias, editor, and Graeve, Lutz, editor

Published
2014
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12. Immune escape pathways from the HBV core18-27 CD8 T cell response are driven by individual HLA class I alleles

Author

Walker, Andreas, primary, Schwarz, Tatjana, additional, Brinkmann-Paulukat, Janine, additional, Wisskirchen, Karin, additional, Menne, Christopher, additional, Alizei, Elahe Salimi, additional, Kefalakes, Helenie, additional, Theissen, Martin, additional, Hoffmann, Daniel, additional, Schulze zur Wiesch, Julian, additional, Maini, Mala K., additional, Cornberg, Markus, additional, Kraft, Anke RM, additional, Keitel, Verena, additional, Bock, Hans H., additional, Horn, Peter A., additional, Thimme, Robert, additional, Wedemeyer, Heiner, additional, Heinemann, Falko M., additional, Luedde, Tom, additional, Neumann-Haefelin, Christoph, additional, Protzer, Ulrike, additional, and Timm, Jörg, additional

Published
2022
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17. Probabilistic Aspects in Classification

Author

Bock, Hans H., Bock, H.-H., editor, Opitz, O., editor, Schader, M., editor, Hayashi, Chikio, editor, Yajima, Keiji, editor, Bock, Hans-Hermann, editor, Ohsumi, Noboru, editor, Tanaka, Yutaka, editor, and Baba, Yasumasa, editor

Published
1998
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19. Immune escape pathways from the HBV core₁₈₋₂₇ CD8 T cell response are driven by individual HLA class I alleles

Author

Walker, Andreas, Schwarz, Tatjana, Brinkmann-Paulukat, Janine, Wisskirchen, Karin, Menne, Christopher, Alizei, Elahe Salimi, Kefalakes, Helenie, Theißen, Martin, Hoffmann, Daniel, Schulze zur Wiesch, Julian, Maini, Mala K., Cornberg, Markus, Kraft, Anke RM, Keitel, Verena, Bock, Hans H., Horn, Peter, Thimme, Robert, Wedemeyer, Heiner, Heinemann, Falko M., Luedde, Tom, Neumann-Haefelin, Christoph, Protzer, Ulrike, and Timm, Jörg

Subjects
Medizin, Biologie
Abstract

Background and aims: There is growing interest in T cell-based immune therapies for a functional cure of chronic HBV infection including check-point inhibition, T cell-targeted vaccines or TCR-grafted effector cells. All these approaches depend on recognition of HLA class I-presented viral peptides. The HBV core region 18-27 is an immunodominant target of CD8+ T cells and represents the prime target for T cell-based therapies. Here, a high-resolution analysis of the core₁₈₋₂₇ specific CD8+ T cell and the selected escape pathways was performed. Methods: HLA class I typing and viral sequence analyses were performed for 464 patients with chronic HBV infection. HBV-specific CD8+ T-cell responses against the prototype and epitope variants were characterized by flow cytometry. Results: Consistent with promiscuous presentation of the core₁₈₋₂₇ epitope, antigen-specific T cells were detected in patients carrying HLA-A*02:01, HLA-B*35:01, HLA-B*35:03 or HLA-B*51:01. Sequence analysis confirmed reproducible selection pressure on the core₁₈₋₂₇ epitope in the context of these alleles. Interestingly, the selected immune escape pathways depend on the presenting HLA-class I-molecule. Although cross-reactive T cells were observed, some epitope variants achieved functional escape by impaired TCR-interaction or disturbed antigen processing. Of note, selection of epitope variants was exclusively observed in HBeAg negative HBV infection and here, detection of variants associated with significantly greater magnitude of the CD8 T cell response compared to absence of variants. Conclusion: The core₁₈₋₂₇ epitope is highly variable and under heavy selection pressure in the context of different HLA class I-molecules. Some epitope variants showed evidence for impaired antigen processing and reduced presentation. Viruses carrying such escape substitutions will be less susceptible to CD8+ T cell responses and should be considered for T cell-based therapy strategies. CA extern

Published
2022

22. Ephrin Bs and canonical Reelin signalling

Author

Pohlkamp, Theresa, Xiao, Lei, Sultana, Rukhsana, Bepari, Asim, Bock, Hans H., Henkemeyer, Mark, and Herz, Joachim

Subjects
Cell interactions -- Research, Neurological research, Ephrin B -- Physiological aspects, Cellular signal transduction -- Research, Neurons -- Physiological aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Theresa Pohlkamp [1]; Lei Xiao [2, 3]; Rukhsana Sultana [2, 3]; Asim Bepari [2, 3]; Hans H. Bock [4]; Mark Henkemeyer [2, 3]; Joachim Herz (corresponding author) [1, 2, [...]

Published
2016
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24. Immune escape pathways from the HBV core18-27 CD8 T cell response are driven by individual HLA class I alleles.

Author

Walker, Andreas, Schwarz, Tatjana, Brinkmann-Paulukat, Janine, Wisskirchen, Karin, Menne, Christopher, Alizei, Elahe Salimi, Kefalakes, Helenie, Theissen, Martin, Hoffmann, Daniel, zur Wiesch, Julian Schulze, Maini, Mala K., Cornberg, Markus, Kraft, Anke R. M., Keitel, Verena, Bock, Hans H., Horn, Peter A., Thimme, Robert, Wedemeyer, Heiner, Heinemann, Falko M., and Luedde, Tom

Subjects
T cells, HISTOCOMPATIBILITY antigens, CD8 antigen, HEPATITIS B, HEPATITIS B virus, ALLELES
Abstract

Background and aims: There is growing interest in T cell-based immune therapies for a functional cure of chronic HBV infection including check-point inhibition, T cell-targeted vaccines or TCR-grafted effector cells. All these approaches depend on recognition of HLA class I-presented viral peptides. The HBV core region 18-27 is an immunodominant target of CD8+ T cells and represents the prime target for T cell-based therapies. Here, a high-resolution analysis of the core18-27 specific CD8+ T cell and the selected escape pathways was performed. Methods: HLA class I typing and viral sequence analyses were performed for 464 patients with chronic HBV infection. HBV-specific CD8+ T-cell responses against the prototype and epitope variants were characterized by flow cytometry. Results: Consistent with promiscuous presentation of the core18-27 epitope, antigen-specific T cells were detected in patients carrying HLA-A*02:01, HLA-B*35:01, HLA-B*35:03 or HLA-B*51:01. Sequence analysis confirmed reproducible selection pressure on the core18-27 epitope in the context of these alleles. Interestingly, the selected immune escape pathways depend on the presenting HLA-class I-molecule. Although cross-reactive T cells were observed, some epitope variants achieved functional escape by impaired TCR-interaction or disturbed antigen processing. Of note, selection of epitope variants was exclusively observed in HBeAg negative HBV infection and here, detection of variants associated with significantly greater magnitude of the CD8 T cell response compared to absence of variants. Conclusion: The core18-27 epitope is highly variable and under heavy selection pressure in the context of different HLA class I-molecules. Some epitope variants showed evidence for impaired antigen processing and reduced presentation. Viruses carrying such escape substitutions will be less susceptible to CD8+ T cell responses and should be considered for T cell-based therapy strategies. [ABSTRACT FROM AUTHOR]

Published
2022
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30. Hospital Mortality and Current Trends in Liver Transplantation in Germany A Systematic Analysis of Standardized Hospital Discharge Data, 2008-2017

Author

Loosen, Sven H., Bock, Hans H., Hellmich, Martin, Knoefel, Wolfram T., Trautwein, Christian, Keitel, Verena, Bode, Johannes G., Neumann, Ulf P., Luedde, Tom, Loosen, Sven H., Bock, Hans H., Hellmich, Martin, Knoefel, Wolfram T., Trautwein, Christian, Keitel, Verena, Bode, Johannes G., Neumann, Ulf P., and Luedde, Tom

Abstract

Background: Liver transplantation (LT) has undergone dynamic developments in recent decades. In Germany, the Federal Joint Committee (G-BA) recently tightened the guidelines regarding the minimum number of transplantations a center should perform annually. The aim of the study presented here, was to analyze recent trends in hospital mortality due to LT in Germany. Methods: Standardized hospital discharge data (2008-2017) from the Federal Statistical Office of Germany were used to establish hospital mortality after LT and case volume distribution among centers performing <20 LT annually (low volume centers, LVC), 20-49 LT (medium volume centers, MVC), and >_ 50 LT (high volume centers, HVC). Results: Data from 9254 LT procedures were evaluated. The annual frequency of LT fell from n = 984 (2008) to n = 747 (2017), and over the same period the hospital mortality for all LT procedures went down from 15.8% to 11.0%. Hospital mortality was associated with age (<16 years: 5.3% to 60-69 years: 17.4%); however, there was no further increase in patients >_ 70 years (16.5%). Univariate analysis revealed association of increased hospital mortality with liver disease etiology, the necessity for relaparotomy, and prolonged mechanical ventilation. The proportion of LT procedures performed in LVC and MVC increased and that in HVC decreased. LVC had higher hospital mortality than MVC/HVC, but this effect was dependent on patient age and disease etiology. Conclusion: Our study showed that differences in mortality rate after LT among centers (LVC vs. MVC/HVC) were dependent on patient age and disease etiology. This should be taken into account when discussing the overall organization of LT in Germany.

Published
2021

35. Lipoprotein receptors in the nervous system

Author

Herz, Joachim and Bock, Hans H.

Subjects
Biochemistry -- Research, Lipoproteins -- Physiological aspects, Proteins -- Receptors, Nervous system -- Physiological aspects, Ligands (Biochemistry) -- Physiological aspects, Cholesterol -- Physiological aspects, Biological sciences
Abstract

The authors review the publications on low-density-lipoprotein receptors. The topics of interest include the roles of lipoprotein receptors in the nervous system and the mechanisms by which these receptors modulate and transmit signals in the brain.

Published
2002

49. Selective Inactivation of Reelin in Inhibitory Interneurons Leads to Subtle Changes in the Dentate Gyrus But Leaves Cortical Layering and Behavior Unaffected

Author

Pahle, Jasmine, primary, Muhia, Mary, primary, Wagener, Robin J, primary, Tippmann, Anja, primary, Bock, Hans H, primary, Graw, Janice, primary, Herz, Joachim, primary, Staiger, Jochen F, primary, Drakew, Alexander, primary, Kneussel, Matthias, primary, Rune, Gabriele M, primary, Frotscher, Michael, primary, and Brunne, Bianka, primary

Published
2019
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50. iRhom2 inhibits bile duct obstruction–induced liver fibrosis

Author

Sundaram, Balamurugan, primary, Behnke, Kristina, additional, Belancic, Andrea, additional, Al-Salihi, Mazin A., additional, Thabet, Yasser, additional, Polz, Robin, additional, Pellegrino, Rossella, additional, Zhuang, Yuan, additional, Shinde, Prashant V., additional, Xu, Haifeng C., additional, Vasilevska, Jelena, additional, Longerich, Thomas, additional, Herebian, Diran, additional, Mayatepek, Ertan, additional, Bock, Hans H., additional, May, Petra, additional, Kordes, Claus, additional, Aghaeepour, Nima, additional, Mak, Tak W., additional, Keitel, Verena, additional, Häussinger, Dieter, additional, Scheller, Jürgen, additional, Pandyra, Aleksandra A., additional, Lang, Karl S., additional, and Lang, Philipp A., additional

Published
2019
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