PhD defence P. (Peifa) Yu

Norovirus is the most common global etiology of diarrheal illness, causing both sporadic and epidemic infection and imposing a substantial health and economic burden. Genetically, this virus is genetically highly diverse, posing a challenge for vaccine development efforts. Moreover, the lack of a robust system for cultivating human norovirus (HuNV) largely impedes our understanding of norovirus biology and pathogenesis, as well as the associated immune response. Currently, no licensed norovirus vaccines are available, thus there is clear need for gaining better understanding of virus-host interactions and to develop novel antiviral treatment against norovirus. In the thesis, we first investigated a nucleoside analogue, 2'-Fluoro-2'-deoxycytidine, that potently inhibits murine norovirus (MNV) replication in macrophages. Moreover, we further pursued this research direction and revealed that LPS restricts MNV replication mainly through NF-kB and JAK-STAT signaling pathway. Interferon-stimulated genes (ISGs) are considered as ultimate antiviral effectors. Thus we subsequently focused on the potential role of several host factors on MNV replication. We showed that guanylate-binding protein 2 (GBP2), RIG-I-like receptors including RIG-I and MDA5 restrict the replication of MNV or HuNV, whereas the viral replicase has a different effects on their antiviral actions. Furthermore, we also revealed the potential regulation of cGAS-STING in response to MNV replication, since these two factors also blunts MNV replication in macrophages. Therefore, our results enhance our insight into the intricacies of host responses to norovirus infection, perhaps allowing improved development of antiviral strategies to combat norovirus infection.

The PhD defences do not take place publicly in the usual way in the Senate Hall at campus Woudestein or in the Professor Andries Querido Room at the Erasmus MC. The candidates will defend their dissertation either in a small group or online.