摘要
Human noroviruses （huNoVs） recognize histo-blood group antigens （HBGAs） as attachment factors, in which genogroup （G） I and GII huNoVs use distinct binding interfaces. The genetic and evolutionary relationships of GII huNoVs under selection by the host HBGAs have been well elucidated via a number of structural studies; however, such relationships among GI NoVs remain less clear due to the fact that the structures of HBGA-binding interfaces of only three GI NoVs with similar binding profiles are known. In this study the crystal structures of the P dimers of a Lewis-binding strain, the GI.8 Boxer virus （BV） that does not bind the A and H antigens, in complex with the Lewis b （Le^b） and Ley antigens, respectively, were determined and compared with those of the three previously known GI huNoVs, i.e. GI.1 Nor- walk virus （NV）, GI.2 FUV258 （FUV） and GI.7 TCH060 （TCH） that bind the A/HILe antigens. The HBGA binding interface of BV is composed of a conserved central binding pocket （CBP） that interacts with the β-galactose of the precursor, and a well-developed Le epitope-bind- ing site formed by five amino acids, including three consecutive residues from the long P-loop and one from the S-loop of the P1 subdomain, a feature that was not seen in the other GI NoVs. On the other hand, the H epitope/acetamido binding site observed in the other GI NoVs is greatly degenerated in BV. These data explain the evolutionary path of GI NoVs selected by the poly- morphic human HBGAs. While the CBP is conserved, the regions surrounding the CBP are flexible, providingfreedom for changes. The loss or degeneration of the H epitope/acetamido binding site and the reinforcement of the Le binding site of the GI,8 BV is a typical example of such change selected by the host Lewis epitope.
Human noroviruses （huNoVs） recognize histo-blood group antigens （HBGAs） as attachment factors, in which genogroup （G） I and GII huNoVs use distinct binding interfaces. The genetic and evolutionary relationships of GII huNoVs under selection by the host HBGAs have been well elucidated via a number of structural studies; however, such relationships among GI NoVs remain less clear due to the fact that the structures of HBGA-binding interfaces of only three GI NoVs with similar binding profiles are known. In this study the crystal structures of the P dimers of a Lewis-binding strain, the GI.8 Boxer virus （BV） that does not bind the A and H antigens, in complex with the Lewis b （Le^b） and Ley antigens, respectively, were determined and compared with those of the three previously known GI huNoVs, i.e. GI.1 Nor- walk virus （NV）, GI.2 FUV258 （FUV） and GI.7 TCH060 （TCH） that bind the A/HILe antigens. The HBGA binding interface of BV is composed of a conserved central binding pocket （CBP） that interacts with the β-galactose of the precursor, and a well-developed Le epitope-bind- ing site formed by five amino acids, including three consecutive residues from the long P-loop and one from the S-loop of the P1 subdomain, a feature that was not seen in the other GI NoVs. On the other hand, the H epitope/acetamido binding site observed in the other GI NoVs is greatly degenerated in BV. These data explain the evolutionary path of GI NoVs selected by the poly- morphic human HBGAs. While the CBP is conserved, the regions surrounding the CBP are flexible, providingfreedom for changes. The loss or degeneration of the H epitope/acetamido binding site and the reinforcement of the Le binding site of the GI,8 BV is a typical example of such change selected by the host Lewis epitope.
基金
The research described in this article was supported by the National Basic Research Program （973 Program） （Nos. 2011CB910304 and 2011CB915501） and the National Natural Science Foundation of China （Grant Nos. 31400639 and 31170702）. The research of Xi Jiang and Ming Tan＇s labs is supported by the US National Institute of Health （R01 AI089634/P01 HD13021 to X.J. and R21 AI092434/ NCRR 8ULITR000077-04 to M.T.）.
