Exosome-mediated human norovirus infection.

Kyle V Todd,Ralph A Tripp,Donna A Macduff

doi:10.1371/journal.pone.0237044

Abstract

Human norovirus (HuNoV) is a leading cause of acute gastroenteritis. Outbreaks normally occur via the fecal-oral route. HuNoV infection is thought to occur by viral particle transmission, but increasing evidence suggests a function for exosomes in HuNoV infection. HuNoV is contained within stool-derived exosomes, and exosome-associated HuNoV has been shown to replicate in human intestinal enteroids. In this study, we examine exosome-associated HuNoV infection of Vero cells and show that exosomes containing HuNoV may attach, infect, and be passaged in Vero cells. These findings support earlier findings and have implications for developing HuNoV disease intervention strategies.

Highlights

Noroviruses (NoVs) are non-enveloped enteric viruses with small capsids that contain positive-sense RNA genomes [1, 2]
A recent study from our group has shown that Vero cells support Human norovirus (HuNoV) infection and replication [12], and as Vero cells are used for the production of a variety of viral vaccines [13], the study was encouraging for potential HuNoV vaccine production
Exosomes from HuNoV-containing stool samples transferred infectious HuNoV to uninfected Vero cells (Table 1) at a level similar to that previously reported for whole stool [12]

Summary

Introduction

Noroviruses (NoVs) are non-enveloped enteric viruses with small capsids that contain positive-sense RNA genomes [1, 2]. NoVs are classified into ten genogroups (GI-GX), with GI, GII, and GIV typically causing the majority of human disease [3]. Human NoVs (HuNoVs) are globally prevalent and often cause self-limiting acute gastroenteritis. GII genotype 4 (GII.4) HuNoVs are a concern because they may cause pandemics giving rise to dominant circulating strains [5,6,7]. Human intestinal enteroids (HIEs) [8] and human Burkitt lymphoma B cells (BJAB cells) [9] have produced encouraging results as HuNoV cell culture models, these substrates are not ideal for vaccine production because HIEs are terminal mixed cell culture systems with a limited lifespan [8, 10] and BJAB cells have been reported to support only a single strain of HuNoV [9, 11]. A recent study from our group has shown that Vero cells support HuNoV infection and replication [12], and as Vero cells are used for the production of a variety of viral vaccines [13], the study was encouraging for potential HuNoV vaccine production

Methods

Results

Conclusion