Unraveling the in vivo host cell tropism and virus dissemination strategies of human norovirus.
Human noroviruses (HuNoVs) are the most common cause of gastroenteritis, resulting in 219,000 deaths/year and a societal cost of $60 billion. The lack of robust small animal models has hindered the understanding of norovirus biology and the development of effective therapeutics. Our team has recently established the most simple and robust HuNoV replication model available to date, by using zebrafish larvae. Since zebrafish larvae are small and optically transparent, we will be able detect exactly where the virus is replicating so we will identify the targeted cells of HuNoV, with a special focus on intestinal and immune cells. There is a knowledge gap on how HuNoV evolves within the host while it replicates, spreads, and faces multiple biological bottlenecks. We will expand this knowledge by quantifying and deep sequencing the viral populations within the identified targeted cells. Immunocompromised individuals infected with HuNoV often experience a chronic gastroenteritis with a very diverse viral population in their stool. Determining whether changes in their genome are linked to a loss of infectivity and how prolonged replication gives rise to divergent viruses will majorly contribute to HuNoV research. Currently, standardized HuNoV research cannot happen since every infection needs to start from a human stool sample containing HuNoV. We aim to produce HuNoV virus stocks for the first time, which will majorly contribute to vaccine and drug development.