The Interactions between Host Glycobiology, Bacterial Microbiota, and Viruses in the Gut

Abstract

Rotavirus (RV) and norovirus (NoV) are the major etiological agents of viral acute gastroenteritis worldwide. Host genetic factors, the histo-blood group antigens (HBGA), are associated with RV and NoV susceptibility and recent findings additionally point to HBGA as a factor modulating the intestinal microbial composition. In vitro and in vivo experiments in animal models established that the microbiota enhances RV and NoV infection, uncovering a triangular interplay between RV and NoV, host glycobiology, and the intestinal microbiota that ultimately influences viral infectivity. Studies on the microbiota composition in individuals displaying different RV and NoV susceptibilities allowed the identification of potential bacterial biomarkers, although mechanistic data on the virus-host-microbiota relation are still needed. The identification of the bacterial and HBGA interactions that are exploited by RV and NoV would place the intestinal microbiota as a new target for alternative therapies aimed at preventing and treating viral gastroenteritis.

Keywords: fucosyltransferase-2 gene (FUT2); histo-blood group antigens (HBGAs); host susceptibility; microbiota; norovirus; rotavirus; secretor.

Figure 1

Biosynthesis routes and schematic structure of histo-blood group antigens (HBGAs) implicated in viral susceptibility. The type-1 (Lacto-N-Biose, LNB) and the type-2 (N-Acetyl-lactosamine, N-Acetyl-Lac) precursors are further elongated by the fucosyltransferase-2 (FUT2) and FUT3 enzymes to produce the H and Lewis antigens, as well as by the A and B enzymes to produce the A and B blood groups.

Figure 2

Proposed interactions of commensal intestinal bacteria with enteric viruses and their effects on viral accessibility and attachment to target cells. Physical interactions of bacteria with enteric viruses can promote or block viral infectivity. The binding of viral particles by bacteria can promote their elimination in the feces, stimulate their attachment to the mucosa or their transcytosis. Alternatively, bacteria can block viral binding sites or modify the glycosylation state of the mucosa, which in turn affects viral attachment. Bacterial components released to the lumen (lipopolysaccharide (LPS) or HBGA-like carbohydrates) have been found to stabilize the virions and enhance their attachment to cells.

Figure 3

Effects on viral infectivity triggered by the cross-talk probiotic–microbiota–host. Bacteria produce diverse molecules that participate in a cross-talk with epithelial or immune cells. This cross-talk triggers diverse mechanisms that impact viral infectivity. Immunoregulation (enhanced production of specific sIgA, cytokines such as IFN-γ or IFN-β or regulation of lymphocyte populations) elicited by bacteria can limit viral infection. The cross-talk enhances the barrier function and induces the synthesis of molecules that can reduce infectivity: mucins, reactive oxygen species (ROS) or certain defensins. At the same time, host mucosal glycosylation is regulated by the endogenous microbiota.