文献类型：期刊文献

英文题名：GII.13/21 Noroviruses Recognize Glycans with a Terminal beta-Galactose via an Unconventional Glycan Binding Site

作者：Cong, Xin[1,2];Sun, Xiao-man[1,2];Qi, Jian-xun[3];Li, Han-bo[1,2,4];Chai, Wen-gang[5];Zhang, Qing[1,2];Wang, Hong[1,2];Kong, Xiang-yu[1,2];Song, Jiao[4];Pang, Li-li[1,2];Jin, Miao[1,2];Li, Dan-di[1,2];Tan, Ming[6,7];Duan, Zhao-jun[1,2]

第一作者：Cong, Xin

通信作者：Duan, ZJ[1];Duan, ZJ[2]

机构：[1]Natl Hlth Commiss Peoples Republ China, Key Lab Med Virol & Viral Dis, Beijing, Peoples R China;[2]China CDC, Natl Inst Viral Dis Control & Prevent, Beijing, Peoples R China;[3]Chinese Acad Sci, Inst Microbiol, Beijing, Peoples R China;[4]Gansu Univ Tradit Chinese Med, Sch Publ Hlth, Lanzhou, Gansu, Peoples R China;[5]Imperial Coll London, Dept Med, Glycosci Lab, London, England;[6]Cincinnati Childrens Hosp Med Ctr, Div Infect Dis, Cincinnati, OH 45229 USA;[7]Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH USA

第一机构：Natl Hlth Commiss Peoples Republ China, Key Lab Med Virol & Viral Dis, Beijing, Peoples R China

通信机构：[1]corresponding author), Natl Hlth Commiss Peoples Republ China, Key Lab Med Virol & Viral Dis, Beijing, Peoples R China;[2]corresponding author), China CDC, Natl Inst Viral Dis Control & Prevent, Beijing, Peoples R China.

年份：2019

卷号：93

期号：15

外文期刊名：JOURNAL OF VIROLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000475793200030)】；

基金：This research was supported by grants from National Science and Technology Major Project (no. 2018ZX10711-001 and no. 2017ZX10104001) and the National Natural Science Foundation of China (NSFC; no. 81472003).

语种：英文

外文关键词：crystal structure; glycan; histo-blood group antigens; human norovirus; viral receptor

摘要：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, nonconventional glycan binding site (GBS) that binds Le(a) antigen. This previous finding raised the question of whether the new GII.13/21 GBS really has 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, nonfat 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 in the control and prevention of NoV-associated diseases. IMPORTANCE Evidence 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 huNoVs in their unconventional glycan binding site. Unlike the previous findings that GII.13/21 genotypes recognize only Le(a) antigen, we found in this study that they can interact with a group of glycans with a 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 the strategy of huNoV control and prevention.