title: Functional and Structural Characterization of P[19] Rotavirus VP8* Interaction with Histo-blood Group Antigens.
abstract: Rotaviruses (RVs) of species A (RVA) are a major causative agent of acute gastroenteritis. Recently, histo-blood group antigens (HBGAs) have been reported to interact with human RVA VP8* proteins. Human P[19] is a rare P genotype of porcine origin that infects humans sporadically. The functional and structural characteristics of P[19] VP8* interaction with HBGAs are unknown. In this study, we expressed and purified the VP8* proteins of human and porcine P[19] RVs. In oligosaccharide and saliva binding assays, P[19] VP8* proteins showed obvious binding to A-, B-, and O-type saliva samples irrespective of the secretor status, implying broad binding patterns. However, they did not display specific binding to any of the oligosaccharides tested. In addition, we solved the structure of human P[19] VP8* at 2.4 Å, which revealed a typical galectin-like fold. The structural alignment demonstrated that P[19] VP8* was most similar to that of P[8], which was consistent with the phylogenetic analysis. Structure superimposition revealed the basis for the lack of binding to the oligosaccharides. Our study indicates that P[19] RVs may bind to other oligosaccharides or ligands and may have the potential to spread widely among humans. Thus, it is necessary to place the prevalence and evolution of P[19] RVs under surveillance.
  
  
  OBJECTIVE
  Human P[19] is a rare P genotype of porcine origin. Based on phylogenetic analysis of VP8* sequences, P[19] was classified in the P[II] genogroup, together with P[4], P[6], and P[8], which have been reported to interact with HBGAs in a genotype-dependent manner. In this study, we explored the functional and structural characteristics of P[19] VP8* interaction with HBGAs. P[19] VP8* showed binding to A-, B-, and O-type saliva samples, as well as saliva of nonsecretors. This implies that P[19] has the potential to spread among humans with a broad binding range. Careful attention should be paid to the evolution and prevalence of P[19] RVs. Furthermore, we solved the structure of P[19] VP8*. Structure superimposition indicated that P[19] may bind to other oligosaccharides or ligands using potential binding sites, suggesting that further investigation of the specific cell attachment factors is warranted.
authors.affiliation: Key Laboratory of Medical Virology and Viral Diseases, Ministry of Health of the People's Republic of China, Beijing, China National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China.
authors.forename: Xiaoman
authors.initials: X
authors.lastname: Sun
authors.affiliation: Key Laboratory of Medical Virology and Viral Diseases, Ministry of Health of the People's Republic of China, Beijing, China National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China.
authors.forename: Dandi
authors.initials: D
authors.lastname: Li
authors.affiliation: Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Ruchao
authors.initials: R
authors.lastname: Peng
authors.affiliation: Key Laboratory of Medical Virology and Viral Diseases, Ministry of Health of the People's Republic of China, Beijing, China National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China.
authors.forename: Nijun
authors.initials: N
authors.lastname: Guo
authors.affiliation: Key Laboratory of Medical Virology and Viral Diseases, Ministry of Health of the People's Republic of China, Beijing, China National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Jin
authors.affiliation: Key Laboratory of Medical Virology and Viral Diseases, Ministry of Health of the People's Republic of China, Beijing, China National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China.
authors.forename: Yongkang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Medical Virology and Viral Diseases, Ministry of Health of the People's Republic of China, Beijing, China National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China.
authors.forename: Guangcheng
authors.initials: G
authors.lastname: Xie
authors.affiliation: Key Laboratory of Medical Virology and Viral Diseases, Ministry of Health of the People's Republic of China, Beijing, China National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Pang
authors.affiliation: Key Laboratory of Medical Virology and Viral Diseases, Ministry of Health of the People's Republic of China, Beijing, China National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Jianxun
authors.initials: J
authors.lastname: Qi
authors.affiliation: Key Laboratory of Medical Virology and Viral Diseases, Ministry of Health of the People's Republic of China, Beijing, China National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China zhaojund@126.com.
authors.forename: Zhao-Jun
authors.initials: ZJ
authors.lastname: Duan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001789:Blood Group Antigens / Q000378:metabolism*; D036022:Capsid Proteins / Q000378:metabolism; D005759:Gastroenteritis / Q000378:metabolism / Q000821:virology; D005838:Genotype; D006801:Humans; D009844:Oligosaccharides / Q000378:metabolism; D010802:Phylogeny; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012401:Rotavirus / Q000378:metabolism*; D012400:Rotavirus Infections / Q000378:metabolism* / Q000821:virology; D016415:Sequence Alignment; D013552:Swine; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D053585:Virus Attachment
chemical_list: D001789:Blood Group Antigens; D036022:Capsid Proteins; D009844:Oligosaccharides; D016601:RNA-Binding Proteins; D017361:Viral Nonstructural Proteins; C079234:NS35 protein, rotavirus