Determinants for Norovirus Host and Cell Tropism

• Applicant: Professor Dr. Stefan Taube
• Subject Area: Virology
• Term: from 2015 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 270957905

Noroviruses, members of the calicivirus family, cause gastrointestinal diseases in various animal species and man. Despite a broad range of hosts, no zoonotic transmissions have been confirmed outside the laboratory and norovirus strains are considered highly species specific. However, recent data shows that zoonosis is feasible. Determinants for host and cell tropism are unknown and research on human noroviruses (HuNoV) has been hampered by the inability to grow the virus in tissue culture. Murine noroviruses (MNV) are the only noroviruses that can be cultivated today. We have a long-standing interest in the structure-function relationship between incoming viral particles and cellular partners during host cell entry. Our published and unpublished data shows that entry is a critical determinant for MNV species specificity. Here, we focus on the interaction of infectious viral particles with surface proteins of susceptible cells. To elucidate determinants of norovirus host and cell tropism, we will identify cellular binding partners of the viral capsid and analyze their role during infection. Recently, we have successfully developed a new small animal model for HuNoV infection, indicating that some HuNoV strains are principally capable of infecting heterologous species. Therefore, we will test stool isolates from patients infected with different HuNoV strains for infection in our mouse model. This will allow us to set-up and further develop our small animal model at the University of Lübeck. Comparing infectious and non-infectious strains, we will be able to identify regions in the norovirus genome responsible for breaking the host barrier. In summary, the results from this study will shed light on the mechanism of norovirus entry. Identifying determinants for host and cell tropism are important containing this emerging virus genus and are of special interest as a target for new anti-norovirus therapeutics, which are currently developed by at the University of Lübeck.

• DFG Programme: Research Grants