title: Sequence analysis of the capsid gene during a genotype II.4 dominated norovirus season in one university hospital: identification of possible transmission routes.
abstract: Norovirus (NoV) is a leading cause of gastroenteritis and genotype II.4 (GII.4) is responsible for the majority of nosocomial NoV infections. Our objective was to examine whether sequencing of the capsid gene might be a useful tool for the hospital outbreak investigation to define possible transmission routes. All NoV positive samples submitted from one university hospital during the 2007/8 season were selected. Genotyping of selected samples by partial polymerase gene sequencing had shown that the majority belonged to the GII.4 variant Den Haag 2006b and had identical polymerase sequences. Sequences of the capsid gene (1412 nucleotides) were obtained from the first available sample from 55 patients. From six immunocompromised patients with persistent infections a second sample was also included. As a control for a point-source outbreak, five samples from a foodborne outbreak caused by the same GII.4 variant were analyzed. Forty-seven of the inpatients (85%) were infected with the GII.4 variant Den Haag 2006b. Phylogenetic analysis of the Den Haag 2006b sequences identified four distinct outbreaks in different departments and a fifth outbreak with possible inter-department spread. In addition, a more heterogeneous cluster with evidence of repeated introductions from the community, but also possible inter-department spread was observed. In all six patients with paired sequences, evidence for in vivo evolution of the virus was found. Capsid gene sequencing showed substantial sequence variation among NoV GII.4 variant Den Haag 2006b strains from one single institution during a nine months' period. This method proved useful to understand the local epidemiology and, when used promptly, has the potential to make infection control measures more targeted.
authors.affiliation: Department of Microbiological Diagnostics and Virology, Statens Serum Institut, Copenhagen, Denmark; Department of Clinical Microbiology, Copenhagen University Hospital Herlev, Herlev, Denmark.
authors.forename: Barbara Juliane
authors.initials: BJ
authors.lastname: Holzknecht
authors.affiliation: Department of Microbiological Diagnostics and Virology, Statens Serum Institut, Copenhagen, Denmark; Research Unit for Clinical Microbiology, University of Southern Denmark, Odense, Denmark.
authors.forename: Kristina Træholt
authors.initials: KT
authors.lastname: Franck
authors.affiliation: Department of Clinical Microbiology, Copenhagen University Hospital Herlev, Herlev, Denmark; Department of Clinical Microbiology, Odense University Hospital, Odense, Denmark.
authors.forename: Rikke Thoft
authors.initials: RT
authors.lastname: Nielsen
authors.affiliation: Department of Microbiological Diagnostics and Virology, Statens Serum Institut, Copenhagen, Denmark; Medical Microbiology, Department of Laboratory Medicine Malmö, Lund University, Malmö, Sweden.
authors.forename: Blenda
authors.initials: B
authors.lastname: Böttiger
authors.affiliation: Department of Microbiological Diagnostics and Virology, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Thea Kølsen
authors.initials: TK
authors.lastname: Fischer
authors.affiliation: Department of Microbiological Diagnostics and Virology, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Jannik
authors.initials: J
authors.lastname: Fonager
mesh_terms: D017250:Caliciviridae Infections / Q000635:transmission* / Q000821:virology; D002213:Capsid / Q000821:virology*; D036022:Capsid Proteins / Q000235:genetics*; D005243:Feces / Q000821:virology; D005759:Gastroenteritis / Q000821:virology*; D014644:Genetic Variation; D016679:Genome, Viral; D006785:Hospitals, University; D006801:Humans; D017720:Molecular Epidemiology; D029322:Norovirus / Q000235:genetics* / Q000302:isolation & purification; D010802:Phylogeny; D017422:Sequence Analysis, DNA
chemical_list: D036022:Capsid Proteins