Characterization of human norovirus binding to gut-associated bacterial ligands

Abstract

Objective Research suggests human norovirus binding to histo-blood group antigen (HBGA)-like molecules on enteric bacteria may enhance viral pathogenesis; however, the properties of these bacterial ligands are not well known. Previous work identified, but did not characterize, seven norovirus-binding bacteria. To further examine this bacteria–virus binding interaction, enteric bacteria were analyzed via Western blot with anti-HBGA antibodies and lectins targeting HBGA-associated sugar components. Virus overlay assays using capsids from six different human norovirus strains further identified responsible ligands and strain dependent binding properties. Results Each bacterial species possessed varying degrees of HBGA-like activity, and lectin binding further elucidated potential sugar residues involved (N-acetyl-galactosamine, α-d-galactose or α-l-fucose). Both GI and GII norovirus capsids bound specific bacterial ligand sizes, and generally corresponded to anti-HBGA Western blot patterns. A 35-kDa band reacted with all HBGA antibodies, bound all six of the noroviruses tested, and had a high affinity for the lectins. Collectively, this work characterizes the varying carbohydrate residues potentially responsible for norovirus–bacteria interactions and provides a basis for future ligand identification.

Interaction of Intestinal Bacteria with Human Rotavirus during Infection in Children

“…Some probiotic and commensal gut bacteria have the ability to in vitro bind RV and human noroviruses [12][13][14][15], and HBGA-like substances have been detected on the surface of enteric species such as Enterobacter cloacae [13], Enterobacter faecium, Klebsiella spp., Citrobacter spp. and Hafnia alvei [16]. The bacterium E. cloacae enhanced norovirus infectivity in gnotobiotic mice and in an in vitro model of infection in human B cells [10].…”

The effect of proteolytic enzymes and pH on GII.4 norovirus, during both interactions and non-interaction with Histo-Blood Group Antigens

“…The protective effect of human gut microbiota could also be involved because it has recently been shown that some enteric bacteria (e.g. Enterobacter cloacae ) bind HuNoVs through the H-like carbohydrates present on the bacterial surface 57 , 58 .…”

A Survey of Analytical Techniques for Noroviruses

“…HBGAs as receptors for HuNoVs can also be further described by the fact that HBGA-expressing bacteria can aid in the cultivation of HuNoVs in a B cell line [32]. In addition, different NoV strains have variable binding abilities to HBGA-expressing bacteria [32][33][34]. Even though almost all HuNoVs bind to HBGAs, some strains of GI VLPs, GII.1 VLPs and GII.14 VLP do not bind to any type of HBGAs nor any saliva [28,35].…”