TRR 60:  Mutual Interaction of Viruses with Cells of the Immune System: From Fundamental Research to Immunotherapy and Vaccination

• Subject Area: Medicine
• Term: from 2009 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 47100475

In the last 8 years the project studied the interaction of the immune system with several different viruses that establish chronic infections in their hosts. These studies provided new concepts of immune regulation and dysregulation in chronic virus infections that can now be utilized for therapeutic approaches and vaccine development. For the next funding period we will exclusively focus on HIV and HBV because therapeutic cure is very rarely achieved for these two chronic infections. The special feature of HBV and retroviruses that makes it so difficult to achieve cure is the reservoir of the virus. Both viruses have persistent forms of their genome, which serve as template for virus production and cannot be targeted by current direct-acting antiviral drugs. Thus, a successful therapy must also address the question of how to tackle the viral reservoir. Now is the time to test novel immunotherapy options, especially combination therapies, in preclinical models of infectious diseases. Some of the possible new targets for immunotherapy were first described to play a role in infectious diseases by PIs of the project. In order to test new tools for immunotherapy against chronic infections sophisticated animal models are needed. It has therefore always been a focus of the TRR60 to develop and improve animal models for chronic virus infections. Basic findings on immune regulation from animal models also need to be confirmed in patient studies, which is why we are analyzing patient samples from very defined large cohorts of HIV- or HBV-infected individuals in almost all our projects. The overall aim of the present project is to develop novel immunotherapies or combination therapies to achieve complete or functional cure of chronic HIV and HBV infections.

• DFG Programme: CRC/Transregios
• International Connection: China

Completed projects

• A02 - The impact of hepatitis C virus on human B cells and its role in B cell lymphoproliferative disorders (Project Heads Dürig, Jan ;  Küppers, Ralf )
• A03 - Activation of Hypoxia Inducible Factor 1 (HIF-1) transcriptional complex during retroviral infection and its role in immune activation (Project Heads Fandrey, Joachim ;  Frede, Stilla )
• A07 - Virale Zweckentfremdung des Proteins DDB1 als Evasionsstrategie gegen angeborene Immunität (Project Heads Le-Trilling, Vu Thuy Khanh ;  Trilling, Mirko )
• B01 - Mechanismen der Evolution des Hepatitis C Virus - Bedeutung der Sequenzvariabilität für die antivirale Immunantwort (Project Heads Hoffmann, Ph.D., Daniel ;  Timm, Jörg )
• B02 - Modulation of T cell function in chronic hepatitis B virus infection - pre-clinical studies in the woodchuck model (Project Head Roggendorf, Michael )
• B04 - Virus-induzierte regulatorische T Zellen in retroviralen Infektionen: Neue Ziele für die Immuntherapie von chronischen Infektionen (Project Heads Bayer, Wibke ;  Dittmer, Ulf ;  Gunzer, Matthias ;  Zelinskyy, Gennadiy )
• B05 - Modulierung spezifischer T Zellantworten gegen das Hepatitis B Virus (HBV) durch PRRs (TLR2 und -13) und PRR Detektion der HBV Infektion (Project Heads Kirschning, Carsten Jürgen ;  Lu, Mengji )
• B07 - The role of the immune system and viral factors for the differential molecular evolution of HIV-1 subtype B/B (Project Heads Bayer, Peter ;  Hoffmann, Ph.D., Daniel )
• B08 - Die Rolle von inhibitorischen Rezeptoren und deren Liganden bei der Immunflucht vor zytotoxischen CD8+ T-Zellen und bei der Etablierung einer chronischen Virusinfektion (Project Head Zelinskyy, Gennadiy )
• B09 - Cytolytic CD4 T cell-mediated viral selection pressure: Defining potential strategies for therapeutic and prophylactic HIV vaccines (Project Head Streeck, Hendrik )
• B10 - The impact of HCV and HIV on human B cells and its role in B cell lymphoproliferative disorders (Project Heads Dürig, Jan ;  Küppers, Ralf )
• C01 - Entwicklung eines neuen Nanopartikel-basierten Impfstoffs zur Behandlung chronisch-persistierender Infektionen (Project Heads Buer, Jan ;  Epple, Matthias ;  Westendorf, Astrid M. )
• C02 - Verbesserung der HIV Env Antikörperantwort durch intrastrukturelle Hilfe von heterologen T-Helfer-Zellen (Project Head Überla, Klaus )
• C06 - Erleichterte Virus Replikation während einer Virusinfektion: Relevanz für Virus Persistenz und Impfung (Project Head Lang, Karl Sebastian )
• C08 - Cytolytic CD4 T cells: Defining potential strategies for therapeutic HIV vaccines (Project Head Streeck, Hendrik )
• Z02 - Zentrales Verwaltungsprojekt (Project Heads Dittmer, Ulf ;  Roggendorf, Michael ;  Yang, Dongliang )
• Z03 - Quantitative und funktionelle Analysen der Proteomveränderungen während chronischer Virusinfektionen (Project Heads Bröring, Ruth ;  Meyer, Helmut Erich ;  Nordhoff, Eckard ;  Schlaak, Jörg Friedrich ;  Sitek, Barbara )

• Applicant Institution: Universität Duisburg-Essen
• Co-Applicant Institution: Fudan University; Huazhong University of Science and Technology; Ruhr-Universität Bochum; Wuhan University
• Partner Organisation: National Natural Science Foundation of China
• Spokespersons: Professor Dr. Ulf Dittmer, since 7/2013; Professor Dr. Michael Roggendorf, until 6/2013