Intestinal Norovirus Binding Patterns in Nonsecretor Individuals

Area of Science:

• Virology
• Immunology
• Gastroenterology

Background:

• Human norovirus (HuNoV) is a leading cause of viral gastroenteritis.
• Secretor individuals, expressing ABO(H) and Lewis histo-blood group antigens (HBGAs), are primarily affected.
• Nonsecretor individuals, lacking secretor antigens but expressing Lewis antigens, are less susceptible but can still be infected.

Purpose of the Study:

• To investigate the interaction of common HuNoV genotypes (GII.3, GII.4, GII.17) with nonsecretor individuals.
• To identify specific antigens involved in HuNoV binding in nonsecretors.
• To explore HuNoV interactions in nonsecretor intestinal tissues, including inflammatory conditions.

Main Methods:

• Use of virus-like particles (VLPs) for HuNoV genotype GII.3, GII.4, and GII.17.
• Saliva binding assays with nonsecretor individuals.
• Analysis of VLP interactions with duodenal and colon tissue blocks from nonsecretor individuals.
• Competition experiments using histo-blood group antigen (HBGA)-specific monoclonal antibodies (MAbs).

Main Results:

• GII.4 HuNoV VLPs specifically interacted with nonsecretor saliva, recognizing the Lewis a (Leª) antigen.
• All three HuNoV genotypes (GII.3, GII.4, GII.17) bound to nonsecretor duodenal tissue, with Leª being the key interaction site.
• HuNoV GII.4 and GII.17 VLPs bound to inflammatory colon tissue from a nonsecretor Crohn's disease patient, mediated by Leª.
• Binding patterns varied, with some genotypes showing restricted interactions in specific tissues.

Conclusions:

• The Lewis a (Leª) antigen plays a pivotal role in HuNoV recognition in nonsecretor individuals.
• Leª is expressed in inflammatory and regenerative intestinal tissues and can mediate HuNoV interactions in nonsecretors.
• The physiological and immunological consequences of HuNoV interactions in nonsecretors require further investigation.