Noroviruses (family Caliciviridae, genus norovirus) are a major cause of gastroenteritis worldwide. Clinical symptoms can last for 2 to 3 days and include vomiting, abdominal cramps, fever, watery diarrhea, headache, chills and myalgia. Symptoms can be much more severe and last longer in people with impaired immune functions and the elderly.
The average incubation period for norovirus-associated gastroenteritis is between 24 and 48 hours post exposure. Norovirus outbreaks occur in a variety of institutional settings (e.g., nursing homes, hospitals, and schools) and affect all age groups. The virus is efficiently transmitted via human-to-human contact, food, and contaminated surfaces.
Noroviruses are highly infectious and extremely stable in the environment (remains infectious after freezing and is insensitive to acidification and heating below 65°C). The increasing globalization of the food industry allows for widespread exposures and presents a risk for recombination between different norovirus strains.
Vaccine candidates have entered human clinical trials, but currently there is no commercial vaccine available.
Known host species
- Humans
- cats
- lions
- dogs
- sheep
- mice
- rats
- cattle
- pigs
Samples used for detection of noroviruses
- Vomit
- Fecal material
- Environmental samples
- Food
- shellfish
- vegetables
- ready-to-eat foods
Genome
The norovirus genome consists of a positive strand ssRNA of approximately 7.500 nucleotides. It contains 3 open reading frames, ORF1, coding for a polyprotein containing a.o. the polymerase, ORF2, coding for the capsid protein(VP1) and ORF3, coding for minor structural protein VP2 (Figure 1).
Figure 1. Norovirus Genome
Nomenclature
Noroviruses are classified into six genogroups (GI to GVI), which are subdivided into genotypes. The most predominant human genotype, II.4, is further subdivided into variants.
Formerly, nomenclature has been based on typing of the ORF2. However noroviruses recombine frequently, mostly at the ORF1/ORF2 junction, complicating nomenclature and genotyping. Therefore, to be able to identify a norovirus, both ORF1 and ORF2 sequences have to be determined and typed1.
Current nomenclature provides the 'P' type, the ORF1 (polymerase) genotype, and the ORF2 (capsid) type. For example, a virus typed as GII.P6-GII.7 contains an ORF1 of the genotype GII.P6 and an ORF2 of the GII.7 genotype. Thus far at least 47 ORF1 and 37 ORF2 genotypes have been described. Some ORF1-ORF2 combinations are more common than others, but novel ORF1-ORF2 combinations are frequently detected. It should be noted that most norovirus sequences available through Genbank have not been typed according to the dual typing system and a large number of sequences have been misclassified.
Commonly, the A, B, C or D region is used for genotyping (Figure 2). Since multiple norovirus genotypes can be found in a single sample (especially in food and environmental samples) we would recommend sequencing of a region overlapping the ORF1/ORF2 junction for correct typing.
Figure 2. Regions used for genotyping of noroviruses (http://www.rivm.nl/mpf/norovirus/typingtool).
Compare reference set
Last update: July 2015
The norovirus reference set comprises one representative per (dual) genotype for all available genotypes of Norovirus, For most genotypes complete genomes have been sequenced. The incomplete genomes are mostly rare genotypes, or genotypes that have been sequenced a long time ago. Where possible, these will be supplemented during the COMPARE project, depending on availability and suitability of the original material.
OF IMPORTANCE: In order to be able to identify norovirus reads in NGS experiments, it is not enough to map or Blast against the official reference sequence in the NCBI reference genome database, NC_001959, the complete genome of Norwalk virus (NoV/GI.P1/GI.1). As the inter genotype level of variation is in the order of 20% on the aminoacid level, the similarity of reads from other genotypes will be too low for a successful Blast or mapping. Even using this extended reference set, Blastp might give better results than Blastn.
All genotypes are also available in an automated typing tool. This tool can be used to type individual sequences (up to 20.000 in batch) but is not yet suitable for the analysis of NGS results (http://www.rivm.nl/mpf/norovirus/typingtool).
1(Kroneman A, Vega E, Vennema H, Vinjé J, White PA, Hansman G, Green K, Martella V, Katayama K, Koopmans M Proposal for a unified norovirus nomenclature and genotyping. Arch Virol. 2013 Oct;158(10):2059-68. doi: 10.1007/s00705-013-1708-5. Epub 2013 Apr 25)