Abstract

Every year, millions of children are infected with viruses that target the gastrointestinal tract, causing acute gastroenteritis and diarrheal illness. Indeed, approximately 700 million episodes of diarrhea occur in children under five annually, with RNA viruses norovirus, rotavirus, and astrovirus serving as major causative pathogens. Numerous methodological advancements in recent years, including the establishment of novel cultivation systems using enteroids as well as the development of murine and other animal models of infection, have helped provide insight into many features of viral pathogenesis. However, many aspects of enteric viral infections remain elusive, demanding further study. Here, we describe the different in vitro and in vivo tools available to explore different pathophysiological attributes of human enteric RNA viruses, highlighting their advantages and limitations depending upon the question being explored. In addition, we discuss key areas and opportunities that would benefit from further methodological progress.

Highlights

  • We discuss the in vitro and in vivo tools that are currently used to study the pathogenesis of human RNA enteric viruses, focusing on norovirus, rotavirus, and astrovirus, to provide a useful compendium for those beginning to explore the field of gastroenteritis (Tables 1 and 2)

  • Human noroviruses (HuNoVs) are non-enveloped, positive-sense RNA viruses in the family Caliciviridae [70], and are the leading cause of acute gastroenteritis worldwide

  • Viral gastroenteritis remains a serious global health concern, as we currently lack vaccines for human noroviruses (HuNoVs) and Human astroviruses (HAstVs), and the efficacy of the RV vaccine may be limited in some countries due to unclear environmental factors

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Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. A diverse group of viral, bacterial, and parasitic pathogens are responsible for acute gastroenteritis, but among these, enteric viruses cause almost half of the cases affecting patients of all ages worldwide, and in the United States, viruses are the leading cause [2]. With the global introduction of the rotavirus vaccine, noroviruses are recognized as the most important cause worldwide of outbreaks of viral gastroenteritis in humans of all age groups [5,6]. We discuss the in vitro and in vivo tools that are currently used to study the pathogenesis of human RNA enteric viruses, focusing on norovirus, rotavirus, and astrovirus, to provide a useful compendium for those beginning to explore the field of gastroenteritis (Tables 1 and 2)

Human RNA Enteric Viruses
Rotavirus
Norovirus
Astrovirus
In Vitro Tools to Study Human Enteric RNA Viruses
Immortalized
Adenocarcinoma
B Cell Lines
Non-Human Primate Cell Lines
Primary Cells
Intestinal Enteroids
In Vivo Tools to Study Human Enteric RNA Viruses
Gnotobiotic Pigs
Mouse Models
Zebrafish
Turkeys
Findings
Conclusions and Future Directions

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