The Role of Host Glycobiology and Gut Microbiota in Rotavirus and Norovirus Infection, an Update

Abstract

Rotavirus (RV) and norovirus (NoV) are the leading causes of acute gastroenteritis (AGE) worldwide. Several studies have demonstrated that histo-blood group antigens (HBGAs) have a role in NoV and RV infections since their presence on the gut epithelial surfaces is essential for the susceptibility to many NoV and RV genotypes. Polymorphisms in genes that code for enzymes required for HBGAs synthesis lead to secretor or non-secretor and Lewis positive or Lewis negative individuals. While secretor individuals appear to be more susceptible to RV infections, regarding NoVs infections, there are too many discrepancies that prevent the ability to draw conclusions. A second factor that influences enteric viral infections is the gut microbiota of the host. In vitro and animal studies have determined that the gut microbiota limits, but in some cases enhances enteric viral infection. The ways that microbiota can enhance NoV or RV infection include virion stabilization and promotion of virus attachment to host cells, whereas experiments with microbiota-depleted and germ-free animals point to immunoregulation as the mechanism by which the microbiota restrict infection. Human trials with live, attenuated RV vaccines and analysis of the microbiota in responder and non-responder individuals also allowed the identification of bacterial taxa linked to vaccine efficacy. As more information is gained on the complex relationships that are established between the host (glycobiology and immune system), the gut microbiota and intestinal viruses, new avenues will open for the development of novel anti-NoV and anti-RV therapies.

Fucosyltransferase 2: A Genetic Risk Factor for Intestinal Diseases

“…Moreover, FUT1 and FUT2 have an apparent difference in acceptor specificity, and two types of H antigen precursors (type 1 and type 2) were regulated by the H enzyme encoded by the FUT2 and FUT1 gene, respectively, i.e., the acceptor specificity of FUT1 is type 2 chains (galactose-β-1→ 4- N -acetyl-glucosamine, N -acetyl-lactosamine) ( GBD 2017 Inflammatory Bowel Disease Collaborators , 2020 ); in contrast, FUT2 gene-specified enzyme is more vigorous on type 1 (galactose-β-1→ 3- N -acetyl-glucosamine, lacto- N -biose) structures (Kyprianou et al, 1990 ). Two kinds of precursors serve as substrates for the FUT2 and FUT1 enzymes, which modify them by attaching an L-fucose to the galactose moiety via an α-1→ 2 linkage, generating type-1 and type-2 H antigens, respectively (Peña-Gil et al, 2021 ). However, if the FUT3 enzyme modifies the precursor, Le a (type 1 precursor) and Le x (type 2 precursor) antigens are produced.…”

“…The second factor affecting enterovirus infection is the host gut microbiome. Similar to IBD, for example, probiotics protect the host from viral infection by modulating the composition of the gut microbiota, enhancing intestinal barrier function, and promoting mucosal immunity (Peña-Gil et al, 2021 ). Additionally, they interfere with the binding of viruses to target cells by blocking viral receptors and binding to the surface in a competitive rejection manner, facilitating their excretion in the feces (Monedero and Rodríguez-Díaz, 2016 ).…”

“…Viral infectivity was reduced to threefold in the presence of R. gauvreauii , indicating that this bacterium has an anti-RV effect (Gozalbo-Rovira et al, 2021 ). Moreover, bacteria belonging to lactobacilli, Mucispirillum, Oscillospira , and Bilophila genera were negatively linked to RV infection in mice (Peña-Gil et al, 2021 ). In fact, the effect of HGBA on bacterial attachment, which may lead to interference with RV infection in vitro .…”

Infant Gut Microbial Metagenome Mining of α- l -Fucosidases with Activity on Fucosylated Human Milk Oligosaccharides and Glycoconjugates

“…In addition, α1,6-linked l -fucose can be also added to the innermost GlcNAc residue in N -glycans constituting the so-called core fucosylation ( 5 ). Fucosylated glycoconjugates play fundamental roles in a wide range of physiological processes, including immune responses, receptor signaling, fertilization, tumor metastasis, and host-microbiome interactions ( 2 , 5 – 8 ). The l -fucose residue is essential in the molecular interactions occurring in many of these processes.…”

The Role of Histo-Blood Group Antigens and Microbiota in Human Norovirus Replication in Zebrafish Larvae

“…Interestingly, HuNoV has a complex relationship with the host microbiome, with both pro- and antiviral effects reported ( 27 ). Certain gut bacterial species also express HBGA-like structures to which HuNoV can attach ( 28 ).…”