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.

Epidemiology of Norovirus Infection Among Immunocompromised Patients at a Tertiary Care Research Hospital, 2010–2013

“…Moreover, nosocomial transmission and outbreaks have been linked to immunodeficient patients [41–43]. Although several patients in our study showed evidence of chronic infection with the same virus genotype over sustained periods, we did not find evidence of transmission of these specific strains within the NIH Clinical Center.…”

Complete Genome Sequence of Human Norovirus GII.4_2006b, a Variant of Minerva 2006

“…A BLAST search revealed 99% identity with multiple GII.4 Den Haag variants from Australia, Japan, Taiwan, and Korea isolated during the 2006 to 2007 period. This result supports the conclusion that closely related GII.4 2006b variants were circulating not only in the United States, but also in multiple areas worldwide in 2006 and 2007 ( 9 – 13 ).…”

Characterization of the Genomic Diversity of Norovirus in Linked Patients Using a Metagenomic Deep Sequencing Approach

“…Overall, we observed that some regions of the NoV genomes are particularly prone to mutation (variant frequency > 5%). It has also been demonstrated that during direct viral transmissions minor variants within the donor viral quasispecies can present as major variants or consensus sequences in the recipient viral population (Kundu et al, 2013 ; Holzknecht et al, 2015 ). Therefore, epidemiological data together with deep WGS data obtained from linked cases and transmission chains can provide efficient means for source attribution and may help to identify signatures and patterns in the mutations throughout the viral genomes.…”