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1. Cell Mediated Immune Response to the Hepatitis C Virus

Author

Rehermann, B., Chisari, F. V., Compans, R. W., editor, Cooper, M., editor, Hogle, J. M., editor, Ito, Y., editor, Koprowski, H., editor, Melchers, F., editor, Oldstone, M., editor, Olsnes, S., editor, Potter, M., editor, Saedler, H., editor, Vogt, P. K., editor, Wagner, H., editor, Hagedorn, Curt H., editor, and Rice, Charles M., editor

Published
2000
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14. R2d2 Drives Selfish Sweeps in the House Mouse.

Author

Didion, JP, Morgan, AP, Yadgary, L, Bell, TA, McMullan, RC, Ortiz de Solorzano, L, Britton-Davidian, J, Bult, CJ, Campbell, KJ, Castiglia, R, Ching, Y-H, Chunco, AJ, Crowley, JJ, Chesler, EJ, Förster, DW, French, JE, Gabriel, SI, Gatti, DM, Garland, T, Giagia-Athanasopoulou, EB, Giménez, MD, Grize, SA, Gündüz, İ, Holmes, A, Hauffe, HC, Herman, JS, Holt, JM, Hua, K, Jolley, WJ, Lindholm, AK, López-Fuster, MJ, Mitsainas, G, da Luz Mathias, M, McMillan, L, Ramalhinho, MDGM, Rehermann, B, Rosshart, SP, Searle, JB, Shiao, M-S, Solano, E, Svenson, KL, Thomas-Laemont, P, Threadgill, DW, Ventura, J, Weinstock, GM, Pomp, D, Churchill, GA, Pardo-Manuel de Villena, F, Didion, JP, Morgan, AP, Yadgary, L, Bell, TA, McMullan, RC, Ortiz de Solorzano, L, Britton-Davidian, J, Bult, CJ, Campbell, KJ, Castiglia, R, Ching, Y-H, Chunco, AJ, Crowley, JJ, Chesler, EJ, Förster, DW, French, JE, Gabriel, SI, Gatti, DM, Garland, T, Giagia-Athanasopoulou, EB, Giménez, MD, Grize, SA, Gündüz, İ, Holmes, A, Hauffe, HC, Herman, JS, Holt, JM, Hua, K, Jolley, WJ, Lindholm, AK, López-Fuster, MJ, Mitsainas, G, da Luz Mathias, M, McMillan, L, Ramalhinho, MDGM, Rehermann, B, Rosshart, SP, Searle, JB, Shiao, M-S, Solano, E, Svenson, KL, Thomas-Laemont, P, Threadgill, DW, Ventura, J, Weinstock, GM, Pomp, D, Churchill, GA, and Pardo-Manuel de Villena, F

Abstract

A selective sweep is the result of strong positive selection driving newly occurring or standing genetic variants to fixation, and can dramatically alter the pattern and distribution of allelic diversity in a population. Population-level sequencing data have enabled discoveries of selective sweeps associated with genes involved in recent adaptations in many species. In contrast, much debate but little evidence addresses whether "selfish" genes are capable of fixation-thereby leaving signatures identical to classical selective sweeps-despite being neutral or deleterious to organismal fitness. We previously described R2d2, a large copy-number variant that causes nonrandom segregation of mouse Chromosome 2 in females due to meiotic drive. Here we show population-genetic data consistent with a selfish sweep driven by alleles of R2d2 with high copy number (R2d2(HC)) in natural populations. We replicate this finding in multiple closed breeding populations from six outbred backgrounds segregating for R2d2 alleles. We find that R2d2(HC) rapidly increases in frequency, and in most cases becomes fixed in significantly fewer generations than can be explained by genetic drift. R2d2(HC) is also associated with significantly reduced litter sizes in heterozygous mothers, making it a true selfish allele. Our data provide direct evidence of populations actively undergoing selfish sweeps, and demonstrate that meiotic drive can rapidly alter the genomic landscape in favor of mutations with neutral or even negative effects on overall Darwinian fitness. Further study will reveal the incidence of selfish sweeps, and will elucidate the relative contributions of selfish genes, adaptation and genetic drift to evolution.

Published
2016

15. The natural history of acute hepatitis C: clinical presentation, laboratory findings, and treatment outcomes

Author

Loomba, R., Rivera, M. M., McBurney, R., Park, Y., Haynes-Williams, V., Rehermann, B., Alter, H. J., Herrine, S. K., Liang, T. J., Hoofnagle, J. H., and Heller, T.

Subjects
Adult, Male, Time Factors, Interferon-alpha, Interferon alpha-2, Middle Aged, Antiviral Agents, Hepatitis C, Severity of Illness Index, Article, Recombinant Proteins, Young Adult, Treatment Outcome, Acute Disease, Ribavirin, Disease Progression, Humans, Drug Therapy, Combination, Female, Aged
Abstract

Acute hepatitis C has variable modes of presentation and frequently results in chronic infection. Its optimal management has yet to be defined.To establish natural history and complications of treatment of acute hepatitis C.Data from all patients presenting with acute hepatitis C to the National Institutes of Health between 1994 and 2007 were reviewed.Twenty-five patients were identified. Symptoms were reported by 80% and jaundice by 40%. Aminotransferase levels and hepatitis C virus (HCV) RNA levels fluctuated greatly; 18% of patients were intermittently negative for HCV RNA. Five patients recovered spontaneously whereas 20 developed chronicity or received interferon-based therapy during the acute phase. Among 15 patients treated during the acute phase with peginterferon with or without ribavirin for 24 weeks, all became HCV RNA negative within 4-8 weeks, and all except two (HIV-positive) achieved a sustained virological response. Side effects (particularly psychiatric) were common and limited treatment in 30%.Among 25 patients with acute HCV infection, fluctuating illness was common and spontaneous recovery occurred in only 20%. Anti-viral treatment with a 24-week course of peginterferon and ribavirin was highly effective, but marked by frequent and severe side effects.

Published
2010

19. Mechanisms of alcoholic liver disease: cytokines

Author

Abe, M., Akbar, S. M. F., Brenner, D. A., Cameron, R. G., Chollet-Martin, S., Cohard, M., Gao, B., Garaud, J. J., Horiike, N., Katz, G. G., Kumagi, T., Maeyama, S., Michitaka, K., Neuman, M. G., Ohata, M., Onji, M., Thierry Poynard, Rehermann, B., Saito, S., Shear, N. H., Taieb, J., Takamatsu, M., Toda, G., Uchikoshi, T., and Yamauchi, M.

Subjects
Liver Cirrhosis, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Polymorphism, Genetic, Alcohol Drinking, Tumor Necrosis Factor-alpha, Interleukins, Medicine (miscellaneous), Hepacivirus, Toxicology, Psychiatry and Mental health, Interferon-gamma, Phosphatidylcholines, Animals, Cytokines, Humans, Mitogen-Activated Protein Kinases, Liver Diseases, Alcoholic, Macrophage Migration-Inhibitory Factors, Protein Kinase C
Abstract

This article represents the proceedings of a workshop at the 2000 ISBRA Meeting in Yokohama, Japan. The chair was Manuela G. Neuman. The presentations were (1) New aspects of hepatic fibrosis, by D. A. Brenner; (2) Cellular immune response in hepatitis C models, by B. Rehermann; (3) The role of interleukin-10 in acute alcoholic hepatitis, by J. Taieb, S. Chollet-Martin, M. Cohard, J. J. Garaud, and T. Poynard; (4) Cytokine-mediated apoptosis in vitro, by M. G. Neuman; (5) Signaling for apoptosis and repair in vitro, by G. G. Katz, R. G. Cameron, N. H. Shear, and M. G. Neuman; (6) Interferons activate the P42/44 mitogen-activated protein kinase and Janus Kinase signal transducers and activation of transcription (JAK-STAT) signaling pathways in hepatocytes: Differential regulation by acute ethanol via a protein kinase C-dependent mechanism, by B. Gao; (7) Genetic polymorphisms of interleukin-1 in association with the development of Japanese alcoholic liver disease, by M. Takamatsu, M. Yamauchi, M. Ohata, S. Saito, S. Maeyama, T. Uchikoshi, and G. Toda; and (8) Increased levels of macrophage migration inhibitory factor in sera from patients with alcoholic liver diseases, by T. Kumagi, S. M. F. Akbar, M. Abe, K. Michitaka, N. Horiike, and M. Onji.

Published
2001

33. Mechanisms of Alcoholic Liver Disease: Cytokines

Author

Neuman, Manuela G., primary, Brenner, D. A., additional, Rehermann, B., additional, Taieb, J., additional, Chollet-Martin, S., additional, Cohard, M., additional, Garaud, J. J., additional, Poynard, T., additional, Katz, G. G., additional, Cameron, R. G., additional, Shear, N. H., additional, Gao, B., additional, Takamatsu, M., additional, Yamauchi, M., additional, Ohata, M., additional, Saito, S., additional, Maeyama, S., additional, Uchikoshi, T., additional, Toda, G., additional, Kumagi, T., additional, Akbar, S. M. F., additional, Abe, M., additional, Michitaka, K., additional, Horiike, N., additional, and Onji, M., additional

Published
2001
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44. Hepatitis C virus (HCV)-specific immune responses of long-term injection drug users frequently exposed to HCV.

Author

Mizukoshi E, Eisenbach C, Edlin BR, Newton KP, Raghuraman S, Weiler-Normann C, Tobler LH, Busch MP, Carrington M, McKeating JA, O'Brien TR, Rehermann B, Mizukoshi, Eishiro, Eisenbach, Christoph, Edlin, Brian R, Newton, Kimberly P, Raghuraman, Sukanya, Weiler-Normann, Christina, Tobler, Leslie H, and Busch, Michael P

Abstract

Background: Injection drug users (IDUs) who successfully clear hepatitis C virus (HCV) have a reduced risk of developing chronic reinfection, despite their continuing exposure to the virus. To identify immunological correlates for this apparent protection, we studied HCV-specific immune responses in long-term IDUs (duration, >10 years).Methods: HCV-specific T cell responses were assessed in proliferation, enzyme-linked immunospot (ELISPOT), interferon (IFN)-gamma secretion, and cytotoxicity assays, whereas HCV-specific antibodies were assessed in enzyme immunoassays (EIAs), chemiluminescent assays, and in vitro neutralization assays.Results: HCV-specific T cell proliferation and IFN-gamma production were more common in nonviremic EIA-positive IDUs (16 [94%] of 17 IDUs) than in viremic EIA-positive IDUs (9 [45%] of 20 IDUs) (P= .003). They were also noted in 16 (62%) of 26 nonviremic EIA-negative IDUs. In contrast, 19 (90%) of 21 viremic IDUs displayed neutralizing antibodies (nAbs), compared with 9 (56%) of 16 nonviremic EIA-positive IDUs (P= .04) and 0 of 24 nonviremic EIA-negative IDUs. Nonviremic IDUs with nAbs were older (P= .0115) than those without nAbs, but these groups did not differ in terms of either injection drug use duration or HCV-specific T cell responses.Conclusion: The reduced risk of HCV persistence in IDUs previously recovered from HCV infection correlated with T cell responses, and prolonged antigenic stimulation appears to be required to maintain humoral responses. [ABSTRACT FROM AUTHOR]

Published
2008
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45. Cellular immune response to the hepatitis C virus.

Author

Rehermann, B.

Subjects
*CELLULAR immunity, *HEPATITIS C
Abstract

Examines the cellular immune response at different stages of hepatitis C virus infection. Virus-host interaction; Immunological correlates of viral clearance; Strength and kinetics of the antiviral immune response.

Published
1998

50. A global scientific strategy to cure hepatitis B

Author

Peter A Revill, Francis V Chisari, Joan M Block, Maura Dandri, Adam J Gehring, Haitao Guo, Jianming Hu, Anna Kramvis, Pietro Lampertico, Harry L A Janssen, Massimo Levrero, Wenhui Li, T Jake Liang, Seng-Gee Lim, Fengmin Lu, M Capucine Penicaud, John E Tavis, Robert Thimme, Fabien Zoulim, Patrick Arbuthnot, Andre Boonstra, Kyong-Mi Chang, Per-Jei Chen, Dieter Glebe, Luca G. Guidotti, Jacques Fellay, Carlo Ferrari, Louis Jansen, Daryl T Y Lau, Anna S Lok, Mala K Maini, William Mason, Gail Matthews, Dimitrios Paraskevis, Jörg Petersen, Barbara Rehermann, Eui-Cheol Shin, Alex Thompson, Florian van Bömmel, Fu-Sheng Wang, Koichi Watashi, Hung-Chih Yang, Zhenghong Yuan, Man-Fung Yuen, Timothy Block, Veronica Miller, Ulrike Protzer, Christian Bréchot, Stephen Locarnini, Marion G Peters, Raymond F Schinazi, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Revill, P. A., Chisari, F. V., Block, J. M., Dandri, M., Gehring, A. J., Guo, H., Hu, J., Kramvis, A., Lampertico, P., Janssen, H. L. A., Levrero, M., Li, W., Liang, T. J., Lim, S. -G., Lu, F., Penicaud, M. C., Tavis, J. E., Thimme, R., Arbuthnot, P., Boonstra, A., Chang, K. -M., Chen, P. -J., Glebe, D., Guidotti, L. G., Fellay, J., Ferrari, C., Jansen, L., Lau, D. T. Y., Lok, A. S., Maini, M. K., Mason, W., Matthews, G., Paraskevis, D., Petersen, J., Rehermann, B., Shin, E. -C., Thompson, A., van Bommel, F., Wang, F. -S., Watashi, K., Yang, H. -C., Yuan, Z., Yuen, M. -F., Block, T., Miller, V., Protzer, U., Brechot, C., Locarnini, S., Peters, M. G., Schinazi, R. F., Zoulim, F., and Gastroenterology and Hepatology

Subjects
medicine.medical_specialty, Hepatitis B virus, Tuberculosis, T-Lymphocytes, [SDV]Life Sciences [q-bio], Circular DNA, Global Health, Virus Replication, Antiviral Agents, Article, 03 medical and health sciences, 0302 clinical medicine, Hepatitis B, Chronic, Chronic hepatitis, medicine, Global health, Animals, Humans, Disease Eradication, Intensive care medicine, Cell Line, Transformed, B-Lymphocytes, Immunity, Cellular, Hepatology, business.industry, Public health, Research, Liver Neoplasms, Remission Induction, Gastroenterology, virus diseases, Hepatitis B, medicine.disease, digestive system diseases, 3. Good health, Disease Models, Animal, 030220 oncology & carcinogenesis, DNA, Viral, Hepatocytes, Position paper, 030211 gastroenterology & hepatology, Immunotherapy, business, Malaria, Forecasting
Abstract

Chronic hepatitis B virus (HBV) infection is a global public health challenge on the same scale as tuberculosis, HIV, and malaria. The International Coalition to Eliminate HBV (ICE-HBV) is a coalition of experts dedicated to accelerating the discovery of a cure for chronic hepatitis B. Following extensive consultation with more than 50 scientists from across the globe, as well as key stakeholders including people affected by HBV, we have identified gaps in our current knowledge and new strategies and tools that are required to achieve HBV cure. We believe that research must focus on the discovery of interventional strategies that will permanently reduce the number of productively infected cells or permanently silence the covalently closed circular DNA in those cells, and that will stimulate HBV-specific host immune responses which mimic spontaneous resolution of HBV infection. There is also a pressing need for the establishment of repositories of standardised HBV reagents and protocols that can be accessed by all HBV researchers throughout the world. The HBV cure research agenda outlined in this position paper will contribute markedly to the goal of eliminating HBV infection worldwide.

Published
2019
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