首页|Functional and structural characterization of Norovirus GII.6 in recognizing histo-blood group antigens

Functional and structural characterization of Norovirus GII.6 in recognizing histo-blood group antigens

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Noroviruses(NoVs)are the primary cause of acute gastroenteritis worldwide.Histo-blood group antigens(HBGAs)are receptors or attachment factors that affect the prevalence and host susceptibility of NoVs.GII.6 NoV is one of the predominant genotypes in humans,which recognizes the type ABO secretor of HBGAs.However,the structural basis of GII.6 NoVs interaction with HBGAs receptors remains elusive.In this study,we investigated the binding features of the GII.6 strain to HBGAs using saliva-and glycan-ELISA assays and characterized the mo-lecular basis of the GII.6 virus that recognizes H disaccharide.We showed that the GII.6 P domain recognized some A and O secretor's saliva samples,most B secretor's saliva samples,and H disaccharide antigen,but did not bind non-secretors'saliva.Further,we determined the crystal structures of GII.6 and its complex with H di-saccharides at 1.7 Å,revealing that the P domain of GII.6 shares the conventional binding interface and mode of GII HBGAs.Single residue mutations at the GII.6-H binding sites could inhibit the binding of GII.6 to HBGAs,demonstrating that the interaction residues were crucial in maintaining NoV-glycan integrity.Finally,structural and sequence analyses showed that the major residues of the GII.6-H interaction were conserved among NoVs in the GII genogroup.Taken together,our study characterized the functional and structural features of GII.6 that allow it to interact with HBGAs,and shed light on NoV evolution,epidemiology,and anti-viral drug development.

Noroviruses(NoVs)Histo-blood group antigens(HBGAs)GII.6 P protein structureH disaccharides

Xin Cong、Han-bo Li、Xiao-man Sun、Jian-xun Qi、Qing Zhang、Zhao-jun Duan、Yong Xu、Wen-lan Liu

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Department of Neurosurgery,Shenzhen Second People's Hospital/the First Affiliated Hospital of Shenzhen University Health Science Center,Shenzhen,518035,China

The Center for Medical Genetics&Molecular Diagnosis,Shenzhen Second People's Hospital/the First Affiliated Hospital of Shenzhen University Health Science Center,Shenzhen,518035,China

Key Laboratory for Medical Virology and Viral Diseases,National Health Commission of the People's Republic of China,Beijing 102206,China

National Institute for Viral Disease Control and Prevention,China CDC,Beijing,102206,China

Institute of Microbiology,Chinese Academy of Sciences,Beijing,100101,China

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National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaGuangdong Basic and Applied Basic Reuter FoundationChina Postdoctoral Science FoundationShenzhen Highlevel Hospital Construction Fund

32100111219340052019A15151102202020M682900

2023

中国病毒学
中国科学院武汉病毒研究所,中国微生物学会

中国病毒学

CSTPCDCSCD北大核心
影响因子:0.393
ISSN:1674-0769
年,卷(期):2023.(1)
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