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.
Highlights
Noroviruses form a genus within the Caliciviridae family that is subdivided into seven genogroups (G) and more than 30 genotypes[1]
This review aims to summarize current knowledge about norovirus tropism, cellular entry, interactions with commensal bacteria, and the application of drop-based microfluidics to the analysis of viral evolution[21,22,23,24]
The identification of multiple norovirus-infected cell types of both epithelial and immunological (e.g. B cells, macrophages, dendritic cells, and T cells) origin represents a shift in the paradigm from the assumed enterocyte-tropic nature of noroviruses to a more inclusive definition of an enterotropic virus: one that encompasses infection of multiple cell types residing in the intestine
Summary
Noroviruses form a genus within the Caliciviridae family that is subdivided into seven genogroups (G) and more than 30 genotypes[1]. Over the past five years, microfluidics has been successfully used to i) grow murine norovirus to identify mutations that support escape from neutralizing monoclonal antibody A6.222, ii) develop a rapid, targeted, and culture-free infectivity assay to determine the efficacy of a neutralizing antibody for murine norovirus[21] with comparable results to plaque-based neutralization assays, iii) detect, quantify, and sequence artifactfree rare recombinant noroviruses in vitro[24] and in vivo[23], providing critical information that cannot be obtained using traditional methods such as phylogenetic studies[127,128] and full genome sequencing[128], and, lastly, iv) simultaneously screen for multiple viruses, including noroviruses, in environmental water samples[129,130]. The microfluidics technology is continually being improved and adapted to a wider array of scientific inquiries[121] and has the potential to become an integral platform for future norovirus research, aiding in studies of norovirus evolution and population dynamics, drug screening, and environmental testing
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