title: Genetic analysis and homology modeling of capsid protein of norovirus GII.14.
abstract: In this study, a more detailed genetic characterization of the VP1 capsid protein of uncommon norovirus (NoV) GII.14 strains reported previously in Japan and China was performed using sequence analyses and homology modeling technique. The result of genetic comparison with the M7 prototype strain of GII.14 revealed that 10 amino acid mutations were observed at the same positions across the P2 and P1-2 subdomains in both Japanese and Chinese strains. By the homology modeling of the P domain, 7 out of these 10 mutations were predicted to be located on the surface-exposed P2 and P1-2 subdomains. All GII.14 strains had an altered RGD-like motif (RGT → KGT). While the Chinese strains contained 5 random amino acid changes in the S domain and the P2 subdomain, these changes were not detected in the Japanese strains. In addition, the histo-blood group antigen (HBGA)-binding interfaces remain identical to those of the previously determined GII.4 structure (VA387), suggesting the conservation of HBGA binding profile within the GII genogroup. Taken together, this report provides supportive structural data that antigenic drifts that occurred mostly in the P2 and P1-2 subdomains might be sufficient to generate new mutants, thus permitting the GII.14 virus to escape the host pre-existing immunity. These results also suggest the need for comparing the evolutionary profiles and structural models of rare NoV genotypes to an insight into NoV evolution.
authors.affiliation: Department of Developmental Medical Sciences, School of International Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Wisoot
authors.initials: W
authors.lastname: Chan-It
authors.forename: Aksara
authors.initials: A
authors.lastname: Thongprachum
authors.forename: Shoko
authors.initials: S
authors.lastname: Okitsu
authors.forename: Masashi
authors.initials: M
authors.lastname: Mizuguchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ushijima
mesh_terms: D000595:Amino Acid Sequence; D036022:Capsid Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002681:China; D016000:Cluster Analysis; D017124:Conserved Sequence; D005838:Genotype; D006801:Humans; D007564:Japan; D008958:Models, Molecular; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000235:genetics; D020125:Mutation, Missense; D029322:Norovirus / Q000187:drug effects* / Q000302:isolation & purification; D010802:Phylogeny; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
chemical_list: D036022:Capsid Proteins; D050505:Mutant Proteins
keywords: P2 domain; genetic diversity; homology modeling; norovirus GII.14