Human noroviruses (huNoVs) that cause epidemic acute gastroenteritis recognize histo-blood group antigens (HBGAs) as host attachment factors affecting host susceptibility. HuNoVs are genetically diverse， containing at least 31 genotypes in the two major genogroups (GI and GII). Three GII genotypes， GII.17/13/21， form a unique genetic lineage， in which GII.17 genotype retains the conventional GII HBGA binding site (HBS)， while GII.13/21 genotypes acquire a completely new HBS. To understand the molecular bases behind these evolutionary changes， we solved the crystal structures of the HBGA-binding protruding domains of 1) an early GII.17 variant (1978) that does not bind or binds weakly to HBGAs， 2) ... More
Human noroviruses (huNoVs) that cause epidemic acute gastroenteritis recognize histo-blood group antigens (HBGAs) as host attachment factors affecting host susceptibility. HuNoVs are genetically diverse， containing at least 31 genotypes in the two major genogroups (GI and GII). Three GII genotypes， GII.17/13/21， form a unique genetic lineage， in which GII.17 genotype retains the conventional GII HBGA binding site (HBS)， while GII.13/21 genotypes acquire a completely new HBS. To understand the molecular bases behind these evolutionary changes， we solved the crystal structures of the HBGA-binding protruding domains of 1) an early GII.17 variant (1978) that does not bind or binds weakly to HBGAs， 2) the new GII.17 variant (2014/15) that binds A/B/H antigens strongly via an optimized GII HBS， and 3) a GII.13 variant (2010) that binds the Lewis-a (Le) antigen via the new HBS. These serial， high resolution structural data enable a comprehensive structural comparison to understand the evolutionary changes of the GII.17/13/21 lineage， including the emergence of the new HBS of the GII.13/21 sublineage and the possible HBS optimization of the recent GII.17 variant for enhanced HBGA binding ability. Our study elucidated the structural adaptations of the GII.17/13/21 lineage through distinct evolutionary paths， which may put forward a theory explaining huNoV adaptations and evolutions.
