6jys

Publication Abstract from PubMed

Human noroviruses (huNoVs) recognize histo-blood group antigens (HBGAs) as host susceptibility factors. GII.13 and GII.21 huNoVs form a unique genetic lineage that emerged from mainstream GII NoVs via development of a new, non-conventional glycan binding site (GBS) that binds Le(a) antigen. This previous finding raised a question whether the new GII.13/21 GBS has really such a narrow glycan binding spectrum. In this study, we provide solid phenotypic and structural evidence indicating that this new GBS recognizes a group of glycans with a common terminal beta-galactose (beta-Gal). First, we found that P domain proteins of GII.13/21 huNoVs circulating at different times bound three glycans sharing a common terminal beta-Gal, including Lec, lactose, and mucin core 2. Second, we solved the crystal structures of the GII.13 P dimers in complex with Lec and mucin core 2, which showed that beta-Gal is the major binding saccharide. Third, non-fat milk and lactose blocked the GII.13/21 P domain-glycan binding, which may explain the low prevalence of GII.13/21 viruses. Our data provide new insight into the host interactions and epidemiology of huNoVs, which would help control and prevention of NoV associated diseases.ImportanceEvidence from both phenotypic binding assay and structural study support the observed interactions of human noroviruses (huNoVs) with histo-blood group antigens (HBGAs) as receptors or attachment factors, affecting their host susceptibility. GII.13 and GII.21 genotypes form a unique genetic lineage that differs from the mainstream GII human noroviruses (huNoVs) in their unconventional glycan binding site. Unlike the previous findings that GII.13/21 genotypes recognize only Le(a) antigen, we found here that they can interact with a group of glycans with common terminal beta-Gal, including Lec, lactose, and mucin core 2. However, this wide glycan binding spectrum in a unique binding mode of the GII.13/21 huNoVs appears not to increase their prevalence, probably due to the existence of decoy glycan receptors in human gastrointestinal tract limiting their infection. Our findings shed light on the host interaction and epidemiology of huNoVs, which would impact on strategy of huNoV control and prevention.

GII.13/21 noroviruses recognize glycans with a terminal beta-galactose via an unconventional glycan binding site.,Cong X, Sun XM, Qi JX, Li HB, Chai WG, Zhang Q, Wang H, Kong XY, Song J, Pang LL, Jin M, Li DD, Tan M, Duan ZJ J Virol. 2019 May 22. pii: JVI.00723-19. doi: 10.1128/JVI.00723-19. PMID:31118252^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.