SFB 1021:  RNA Viruses: RNA Metabolism, Host Response and Pathogenesis

Virus infections remain a major threat to human and animal health. They have a huge impact on global economies and account for a substantial part of healthcare costs worldwide. RNA viruses are of particular interest because their replication machinery generally lacks proofreading activity and this can lead to the emergence of new pathogenic variants that transmit and replicate efficiently in new hosts. A prominent example for this phenomenon is the current COVID-19 pandemic which is caused by SARS-CoV-2, an RNA virus of the Coronaviridae family. The CRC 1021 investigates RNA viruses from different families including highly pathogenic (often zoonotic) viruses causing, for example, hemorrhagic fever, encephalitis or acute respiratory distress syndrome. Research in the CRC 1021 is performed in three major project areas: (i) synthesis and metabolism of viral RNA, (ii) viral factors determining pathogenicity of RNA viruses, and (iii) cellular responses to RNA virus infections and viral factors that counteract or help escape these cellular responses. The planned studies are based on the extensive RNA virus expertise available in this consortium including the availability, generation and use of genetically closely related viruses or nearly identical variants of the same virus (pathotypes) with fundamentally different pathogenic properties in specific hosts. The CRC 1021 employs a wide range of advanced methods and technologies (involving genomics and proteomics analyses) to study these viruses and to obtain new insight into fundamental aspects of RNA virus replication as well as the diverse and dynamic interactions of viral factors with cellular pathways and regulatory networks that operate at the virus-host interface and determine the pathogenicity of RNA viruses in humans and animals. To achieve these goals, the CRC 1021 takes a multi-disciplinary approach that brings together researchers with a highly complementary combination of technical skills and scientific expertise in the fields of RNA virology, cell biology, biochemistry, allergology, pharmaceutical sciences, and pharmacology.

DFG Programme Collaborative Research Centres

• A01 - Replication of large RNA virus genomes: key enzymes and mechanisms (Project Head Ziebuhr, John )
• A02 - Mechanisms and regulation of Ebola virus RNA synthesis (Project Heads Becker, Stephan ;  Biedenkopf, Nadine ;  Hartmann, Roland K. )
• A03 - Control of Hepatitis C Virus replication by viral and cellular factors (Project Head Niepmann, Michael )
• A04 - Role of the RNA modifications 2'-O-methylation and N6-methyladenosine in viral pathogenicity (Project Head Bauer, Stefan )
• A05 - Intracellular organization of Ebola virus RNA synthesis; formation, maturation and transport of viral RNP (Project Head Becker, Stephan )
• B01 - Pathogenesis of feline infectious peritonitis (Project Heads Tekes, Gergely ;  Thiel, Heinz-Jürgen ;  Ziebuhr, John )
• B02 - Role of receptor specificity and membrane fusion activity of influenza viruses in host range, cell tropism and pathogenicity (Project Heads Bauer, Stefan ;  Matrosovich, Ph.D., Mikhail )
• B03 - Adaptation of Marburg virus to rodents as a model to study viral pathogenesis: Response of the mononuclear phagocyte system (Project Head Becker, Stephan )
• B04 - Nipah virus replication in respiratory epithelial cells (Project Head Maisner, Andrea Susanne )
• B05 - Lassa virus: host cell tropism and molecular pathogenesis (Project Head Strecker, Thomas )
• B06 - Functional comparison of the NSs virulence factors from the genus Phlebovirus (Project Head Weber, Friedemann )
• B07 - The protease specificity of influenza virus hemagglutinin and coronavirus spike protein with monobasic cleavage site: underlying mechanisms and host proteases involved (Project Head Böttcher-Friebertshäuser, Eva )
• B08 - Structural and functional factors determining entry and replication of hepatitis D and B viruses during co-infection (Project Heads Geyer, Joachim ;  Glebe, Dieter )
• B09 - Morbillivirus Intra- and Inter-Host Dynamics and Genetic Plasticity (Project Head von Messling, Veronika )
• B10 - Function of lipid droplets in replication and pathogenesis of neurotropic flaviviruses (Project Head Herker, Eva )
• B11 - Molecular basis for the virulence of Deformed wing virus (DWV) infections in honey bees (Project Head Lamp, Benjamin )
• B12 - Mechanistic insights into morbillivirus-induced immunosuppression and antiviral responses (Project Heads Pfaller, Christian ;  Sawatsky, Ph.D., Bevan )
• C01 - The impact of influenza virus genome variability on host cell kinase networks and the anti-viral response (Project Heads Pleschka, Stephan ;  Schmitz, M. Lienhard )
• C02 - Regulation of RNA metabolism, translation and protein degradation pathways in the host response to coronavirus infection (Project Head Kracht, Michael )
• C04 - RNA viruses induce heterologous immune protection from atopy and asthma (Project Heads Renz, Harald ;  Skevaki, Chrysanthi )
• C05 - Impact of virus and host factors on lung epithelial cell injury and repair in severe viral pneumonia (Project Head Herold, Ph.D., Susanne Valerie )
• Z01 - Central Tasks (Project Head Becker, Stephan )
• Z02 - Central resource facility for virus genomics and host transcriptomics (Project Heads Chakraborty, Trinad ;  Hain, Torsten ;  Wilhelm, Jochen )
• Z03 - Central resource facility for (quantitative) proteomics applications of RNA-virus infected cells (Project Heads Kracht, Michael ;  Linne, Ph.D., Uwe )

Applicant Institution Philipps-Universität Marburg

Participating University Justus-Liebig-Universität Gießen

Participating Institution Paul-Ehrlich-Institut
Bundesinstitut für Impfstoffe und biomedizinische Arzneimittel

Spokesperson Professor Dr. Stephan Becker