Structural Basis of Glycan Recognition in Globally Predominant Human P[8] Rotavirus

• 来源期刊: 中国病毒学
• 年，卷（期）: 2020,（2）
• 页码范围: 156-170
• 页数: 15页
• 语种: 英文

摘要

Rotavirus (RV) causes acute gastroenteritis in infants and children worldwide.Recent studies showed that glycans such as histo-blood group antigens (HBGAs) function as cell attachment factors affecting RV host susceptibility and prevalence.P[8] is the predominant RV genotype in humans,but the structural basis of how P[8] RVs interact with glycan ligands remains elusive.In this study,we characterized the interactions between P[8] VP8*s and glycans which showed that VP8*,the RV glycan binding domain,recognized both mucin core 2 and H type 1 antigens according to the ELISA-based oligosaccharide binding assays.Importantly,we determined the structural basis of P[8] RV-glycans interaction from the crystal structures of a Rotateq P[8] VP8* in complex with core 2 and H type 1 glycans at 1.8 (A) and 2.3 (A),respectively,revealing a common binding pocket and similar binding mode.Structural and sequence analysis demonstrated that the glycan binding site is conserved among RVs in the P[II] genogroup,while genotype-specific amino acid variations determined different glycan binding preference.Our data elucidated the detailed structural basis of the interactions between human P[8] RVs and different host glycan factors,shedding light on RV infection,epidemiology,and development of anti-viral agents.