Recent advances in understanding noroviruses

Abstract

Noroviruses are the leading cause of acute gastroenteritis around the world. An individual living in the United States is estimated to develop norovirus infection five times in his or her lifetime. Despite this, there is currently no antiviral or vaccine to combat the infection, in large part because of the historical lack of cell culture and small animal models. However, the last few years of norovirus research were marked by a number of ground-breaking advances that have overcome technical barriers and uncovered novel aspects of norovirus biology. Foremost among them was the development of two different in vitro culture systems for human noroviruses. Underappreciated was the notion that noroviruses infect cells of the immune system as well as epithelial cells within the gastrointestinal tract and that human norovirus infection of enterocytes requires or is promoted by the presence of bile acids. Furthermore, two proteinaceous receptors are now recognized for murine norovirus, marking the first discovery of a functional receptor for any norovirus. Recent work further points to a role for certain bacteria, including those found in the gut microbiome, as potential modulators of norovirus infection in the host, emphasizing the importance of interactions with organisms from other kingdoms of life for viral pathogenesis. Lastly, we will highlight the adaptation of drop-based microfluidics to norovirus research, as this technology has the potential to reveal novel insights into virus evolution. This review aims to summarize these new findings while also including possible future directions.

Comparison between patients with norovirus‐related gastroenteritis and asymptomatic carriers with respect to distribution of antibody‐complexed viral particles and intestinal flora

“…The influence of the intestinal flora on norovirus infection was previously reported . However, a comparison with asymptomatic carriers had not been performed.…”

“…This result was based on analyzing the same points in the time course after consumption of contaminated foods. Any association between the detected intestinal flora and significant differences in patient symptoms had not been adequately addressed in previous studies of norovirus‐related gastroenteritis . The characteristics of asymptomatic carriers have long been unclear owing to a deficiency in specimen collection.…”

“…[14][15][16][17][18] However, a comparison with asymptomatic carriers had not been performed. In previous reports, [14][15][16][17][18] commensal bacteria were found to enhance enteric virus infection. 15 Histo-blood group antigen (HBGA)-expressing bacteria were suspected to protect norovirus infections owing to their binding ability.…”

“…Any association between the detected intestinal flora and significant differences in patient symptoms had not been adequately addressed in previous studies of norovirus-related gastroenteritis. [14][15][16][17][18] The characteristics of asymptomatic carriers have long been unclear owing to a deficiency in specimen collection. In contrast, the present findings suggest that asymptomatic carriers with norovirus infection share common characteristics.…”

The Dual Tropism of Noroviruses

“…These include the cloning of the Norwalk virus genome (5), the discovery of murine norovirus (MNV) and establishment of MNV cell culture and mouse models (6,7), and the development of two cell culture systems and multiple animal models for HuNoVs (8)(9)(10)(11)(12)(13). However, robust replication models that enable multigenerational passaging of HuNoVs are still lacking (14). A greater understanding of the cell type(s) infected by HuNoVs (i.e., viral tropism) may promote the development of improved cell culture systems, enabling the generation of cell culture-derived virus stocks.…”