title: Genetic diversity of noroviruses in Chinese adults: potential recombination hotspots and GII-4/Den Haag-specific mutations at a putative epitope.
abstract: Little is known about the role of noroviruses (NVs) in sporadic cases of acute gastroenteritis in adults. The GII-4 NVs are currently the globally dominant genotype with diverse genetic makeups. The mechanism(s) underlying the persistence and rapid evolution of the viruses are not yet clear. In this study we collected 547 specimens from adult of >14 years of age with acute gastroenteritis in Beijing, China from September 2007 to Febraury 2008. NVs were screened and sequenced to determine their genotypes. Bioinformatics methods were used to detect NV recombination and their breakpoints. The residue variations of the capsid proteins between GII-4/Den Haag and previous predominant variants of GII-4 were compared to identify mutations that are likely important for current epidemic wave. Putative epitopes were predicted based upon the crystal structure. 106 (19.4%) NVs were identified among 547 specimens. While GII-4 remains predominant, at least six other genotypes were observed. Two recombinant types were identified with both predicted breakpoints locating within the 24-27 bp region upstream the start codon of ORF2. We found the emergent mutations H414P/Q of the capsid protein are specific for GII-4/Den Haag and this site lies within a predicted antibody-binding epitope. Our data demonstrated that NVs were an important cause of acute gastroenteritis in Chinese adults. The shared breakpoints identified in the GI and GII recombinants imply the presence of recombination hotspots in NVs. The mutations at residue 414 and its location within a putative antigenic epitope suggested a possible mechanism that may allow GII-4 NVs to escape from herd immunity.
authors.affiliation: State Key Laboratory for Molecular Virology and Genetic Engineering, National Institute for Viral Disease Control and Prevention, China CDC, Beijing 100052, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Jin
authors.forename: Jinan
authors.initials: J
authors.lastname: Chen
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Zhang
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.forename: Hui-Ying
authors.initials: HY
authors.lastname: Li
authors.forename: Wei-Xia
authors.initials: WX
authors.lastname: Cheng
authors.forename: Na
authors.initials: N
authors.lastname: Liu
authors.forename: Ming
authors.initials: M
authors.lastname: Tan
authors.forename: Taijiao
authors.initials: T
authors.lastname: Jiang
authors.forename: Zhao-Jun
authors.initials: ZJ
authors.lastname: Duan
mesh_terms: D000328:Adult; D000956:Antigens, Viral / Q000737:chemistry / Q000235:genetics; D017250:Caliciviridae Infections / Q000453:epidemiology / Q000276:immunology / Q000821:virology; D036022:Capsid Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D002681:China / Q000453:epidemiology; D018985:Epitopes, B-Lymphocyte / Q000737:chemistry / Q000235:genetics; D019143:Evolution, Molecular; D005759:Gastroenteritis / Q000453:epidemiology / Q000276:immunology / Q000821:virology; D014644:Genetic Variation; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D029322:Norovirus / Q000145:classification / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification; D010802:Phylogeny; D015995:Prevalence; D011995:Recombination, Genetic
chemical_list: D000956:Antigens, Viral; D036022:Capsid Proteins; D018985:Epitopes, B-Lymphocyte