A robust human norovirus replication model in zebrafish larvae

Human noroviruses (HuNoVs) are an important cause of epidemic and endemic acute gastroenteritis worldwide; annually about 700 million people develop a HuNoV infection resulting in ∼219,000 deaths and a societal cost estimated at 60 billion US dollars 1. The lack of robust small animal models has significantly hindered the understanding of norovirus biology and the development of effective therapeutics against HuNoV. Here we report that HuNoV GI and GII replicate to high titers in zebrafish (Danio rerio) larvae; replication peaks at day 2 post infection and is detectable for at least 6 days. HuNoV is detected in cells of the hematopoietic lineage, the intestine, liver and pancreas. Antiviral treatment reduces HuNoV replication by >2 log10, showing that this model is suited for antiviral studies. Downregulation of fucosyltransferase 8 (fut8) in the larvae reduces HuNoV replication, highlighting a common feature with infection in humans. Zebrafish larvae constitute a simple and robust replication model that will largely facilitate studies of HuNoV biology and the development of antiviral strategies.

Ikonische Prägnanz von Schrift und die Prägung der Überlieferung

Editing Middle High German texts today is led much more by the ventilation of practical necessities than by theoretical consideration. Especially lacking discussions of a basic concept of ›text‹ raises the risk of developing blind spots. The article will try to identify these blind spots as places where the traditional strategy of editing texts on the basis of the faulty-replication model persists. This will be illustrated by new editions of the ›Wunderer‹ and the ›Rosengarten‹. Furthermore, the article evolves a semiotic model of the philological praxis of editing Middle High German heroic epics.