The program comprises 7 major subthemes - 4 projects, 2 specific cores and one technical development program. The leader of each team has specific expertise in one area of clinical medicine, immunology, cell biology and/or molecular biology. Each on their own has made a significant contribution to the bigger picture of viral pathogenesis in hepatitis C. The key feature of this consortium is that these have been blended to create a scientific team which is more than the sum of its parts, as will be detailed below. Specifically we propose to:- 1. Define the role of the hepatocyte as a key player in innate and adaptive immune responses (Project 1 Chung) 2. Define the specific qualities of tissue homing T cell populations in relation to hepatitis C infection (Project 2, Klenerman). 3. Define the functional capacity of intrahepatic T cell populations in persistent infection (Project 3, Lauer/Wherry). 4. Define the impact of T cell selection pressure on viral sequence evolution and the fitness landscape (Project 4, Allen/Henn). 5. Create a panel of reagents to modulate the surface signaling platform of T cells and antigen presenting cells (Core C/Freeman). 6. Create a library of tissue and cells from well defined clinical cohorts for experimental use (Core D/Misradji). 7. Develop a platform technology to examine and modulate critical signaling pathways that limit the adaptive immune response (TDP/Haining).
Hepatitis C virus (HCV) is a major global health problem. Nearly 170 million people worldwide are infected and a substantial fraction of these will develop chronic liver disease, leading to cirrhosis, liver failure and liver cancer. Current therapies are imperfect and expensive, and no vaccine exists. However, there is ample evidence that the immune system plays a critical role in protection against chronic infection. Thus in its own right Hepatitis C virus is a critical target for research, with the aim of developing improved understanding of the virus and immunology, leading to improved therapies and interventions.
| Yu, Wen-Han; Cosgrove, Cormac; Berger, Christoph T et al. (2018) ADCC-Mediated CD56DIM NK Cell Responses Are Associated with Early HBsAg Clearance in Acute HBV Infection. Pathog Immun 3:2-18 |
| Johnson, John L; Georgakilas, Georgios; Petrovic, Jelena et al. (2018) Lineage-Determining Transcription Factor TCF-1 Initiates the Epigenetic Identity of T Cells. Immunity 48:243-257.e10 |
| Gordon, Claire L; Hutchings, Claire L; Highton, Andrew J et al. (2018) Memory inflation following adenoviral vaccination depends on IL-21. Vaccine 36:7011-7016 |
| Carty, Shannon A; Gohil, Mercy; Banks, Lauren B et al. (2018) The Loss of TET2 Promotes CD8+ T Cell Memory Differentiation. J Immunol 200:82-91 |
| Gordon, Claire Louse; Lee, Lian Ni; Swadling, Leo et al. (2018) Induction and Maintenance of CX3CR1-Intermediate Peripheral Memory CD8+ T Cells by Persistent Viruses and Vaccines. Cell Rep 23:768-782 |
| Duan, Xiaoqiong; Li, Shilin; Holmes, Jacinta A et al. (2018) MicroRNA 130a Regulates both Hepatitis C Virus and Hepatitis B Virus Replication through a Central Metabolic Pathway. J Virol 92: |
| Bengsch, Bertram; Ohtani, Takuya; Khan, Omar et al. (2018) Epigenomic-Guided Mass Cytometry Profiling Reveals Disease-Specific Features of Exhausted CD8 T Cells. Immunity 48:1029-1045.e5 |
| Liu, Xiao; Duan, Xiaoqiong; Holmes, Jacinta A et al. (2018) A novel lncRNA regulates HCV infection through IFI6. Hepatology : |
| Chen, Gang; Huang, Alexander C; Zhang, Wei et al. (2018) Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response. Nature 560:382-386 |
| Ussher, James E; Willberg, Christian B; Klenerman, Paul (2018) MAIT cells and viruses. Immunol Cell Biol 96:630-641 |
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