Intestinal norovirus binding patterns in non-secretor individuals

Abstract

Human norovirus (HuNoV) infection is associated with active FUT2 gene, which characterizes the secretor phenotype. However, non-secretor individuals are also affected by HuNoV infection although in a lesser proportion. Here, we study GII.3, GII.4 and GII.17 HuNoV interactions in non-secretor individuals using virus-like particles (VLPs). Only GII.4 HuNoV specifically interacted with non-secretor saliva. Competition experiments using HBGA-specific mAbs demonstrate that GII.4 VLPs recognized the Lewis a antigen (Lea). We also analyzed HuNoV VLP interactions on duodenum tissue blocks from healthy non-secretor individuals. VLP binding was observed for the three HuNoV genotypes in 10 of the 13 individuals, and competition experiments demonstrated that VLP recognition was driven by interaction with the Lea antigen. In 3 individuals, binding was restricted to either GII.4 alone or GII.3 and GII.17. Finally, we performed a VLP binding assay on proximal and distal colon tissue blocks from a non-secretor patient with Crohn’s disease. VLP binding to inflammatory tissues was genotype-specific since GII.4 and GII.17 VLPs were able to interact with regenerative mucosa whereas GII.3 VLP was not. Binding of GII.4 and GII.17 HuNoV VLPs was linked to Lea in regenerative mucosae from the proximal and distal colon. Overall, our data clearly showed that Lea has a pivotal role in the recognition of HuNoV in non-secretors. We also showed that Lea is expressed in inflammatory/regenerative tissues and interacts with HuNoV in a non-secretor individual. The physiological and immunological consequences of such interactions in non-secretors has yet to be elucidated.