Determinants for Norovirus Host and Cell Tropism
Final Report Abstract
Noroviruses that belong to the calicivirus family, are responsible for most gastroenteritis diseases in humans and animals. Despite a wide range of hosts, no zoonotic transmissions of the virus outside the laboratory have been confirmed so far. Overall, noroviruses are therefore highly species-specific. Host criteria and cell tropism were not known at the time of this project and murine noroviruses (MNV) were the only noroviruses that could be efficiently grown in cell culture. One goal of this project was to identify and characterize essential host factors using ligand-based receptor capture (LRC). This part of the project could only be completed as a proof-of-principle. Only the already known cellular receptor of feline calicivirus (FCV) could be successfully verified with the help of LRC, but an analogous experiment with the murine norovirus MNV-1 was unsuccessful and the cellular receptor CD300LF was later identified by Orchard et al. Described in 2016. Studies on the biology of human noroviruses (HuNoV) were severely limited at the beginning of these studies due to the lack of a robust cell culture system or an established small animal model. So far, HuNoV could only be bred in large animal models such as chimpanzees, gnotobiotic pigs and calves, as well as a mouse model with a compromised immune system. In collaboration with Joana Rocha Pereira from the University of Leuven, we have also succeeded in cultivating human noroviruses in the zebrafish model Danio rerio by means of microinjection at the University of Lübeck. Two-day-old zebrafish larvae were robustly infected by microinjection with human noroviruses from stool suspension. Efficient virus replication was demonstrated by RealTime PCR 2-3 days after infection. Furthermore, it was shown that the system is well suited to investigate the antiviral effect and toxicity of small molecules.
Publications
- Open Sesame: New Keys to Unlocking the Gate to Norovirus Infection. Cell Host Microbe. 2018 Oct 10;24(4):463-465
Lingemann M, Taube S
(See online at https://doi.org/10.1016/j.chom.2018.09.018) - Infection of zebrafish larvae with human norovirus and evaluation of the in vivo efficacy of small-molecule inhibitors. Nat Protoc. 2021 Apr;16(4):1830-1849
Van Dycke J, Cuvry A, Knickmann J, Ny A, Rakers S, Taube S, de Witte P, Neyts J, Rocha-Pereira J
(See online at https://doi.org/10.1038/s41596-021-00499-0)
