Work

A robust human norovirus replication model in zebrafish larvae

Year: 2019

Type: article

Abstract: Human noroviruses (HuNoVs) are the most common cause of foodborne illness, with a societal cost of $60 billion and 219,000 deaths/year.The lack of robust small animal models has significantly hindered the understanding of norovirus biology and the development of effective therapeutics.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.The virus (HuNoV GII.4) could be passaged from larva to larva two consecutive times.HuNoV is detected in cells of the hematopoietic lineage and the intestine, supporting the notion of a dual tropism.Antiviral treatment reduces HuNoV replication by >2 log 10 , showing that this model is suited for antiviral studies.Zebrafish larvae constitute a simple and robust replication model that will largely facilitate studies of HuNoV biology and the development of antiviral strategies. Author summaryHuman norovirus (HuNoV) is the number one agent of viral gastroenteritis worldwide.It can infect people of all age groups, resulting in 700 million infections and 219,000 deaths each year.Outbreaks of acute HuNoV gastroenteritis occur often, but chronic infections also happen in people with immune deficiencies.Despite its clinical relevance, studying the virus has been a decades-long challenge because no simple and efficient cultivation system existed.This has recently started to change; we here contribute with an important step forward by establishing an in vivo model system to study HuNoV replication using zebrafish larvae.We inject a HuNoV in the yolk (food reserve) of 3-day-old zebrafish larvae, which results in high virus titers up to 6 days after inoculation.We could detect the

Source: PLoS Pathogens

DOI: 10.1371/journal.ppat.1008009