Norovirus Classification

Noroviruses belong to a genus of genetically diverse viruses within the family Caliciviridaewhich are responsible for acute gastroenteritis in humans and animals. As viral culture system is not available, genetic analysis represents the principal method to classify norovirus strains. These viruses can be subdivided into genogroups, each of which further segregates into genotypes.

The lack of an internationally approved standard for norovirus nomenclature and definition of genotypes has resulted in some conflicting reports in the medical literature. As global distribution of these agents is becoming increasingly important, it is pivotal to establish a standardized nomenclature in order to adequately address epidemiologically important lineages.

Principles of classification

Historically, the classification of noroviruses was based on cross-challenge research studies in volunteers and cross-reactivity analysis by immune electron microscopy. Such antigenic classification schemes did not exhibit adequate accuracy and reproducibility, which were attributed to the cross-reactivity of antibodies.

Today the classification is most commonly based on the nucleotide sequence of the open reading frame 2 (ORF2), which encodes the major structural capsid protein. They can be subdivided into six genogroups (GI-GVI), consisting of at least 32 genetic clusters or genotypes. There are 8 genotypes in GI genogroup, 17 genotypes in GII genogroup, 2 genotypes in GIII genogroup, and one genotype for each of the other three genogroups.

Correct classification is important particularly for noroviruses belonging to genogroup II, genotype 4 (GII.4), due to the emergence of new pandemic GII.4 variants. Molecular epidemiologic studies have shown that 70% of norovirus outbreaks are caused by this variant genotype. GII.4 strains frequently undergo genetic change and these transformed forms are sometimes called "variants" or "subtypes".Most noroviruses affecting humans belong to GI or GII, which are the genogroups with the largest genetic diversity. GIV can be also found in humans, while GIII and GV strains are found in cows and mice, respectively. Canine norovirus is a recently discovered pathogen in dogs, with strains classified into genogroups IV and VI.

Unified norovirus nomenclature

Cryptograms for noroviruses (akin to influenza classification) would undoubtedly facilitate communication by inclusion of the genogroup, genotype and variant assignment. The strain name should include the organism (norovirus GI-VI), host (human, porcine, bovine, etc.), country code (ISO), year of sampling, genogroup and genotype and variant name (city, if necessary followed by a serial number).

Some examples are norovirus GII/Hu/US/2010/GII.P12-GII.12/HS206norovirus,norovirus GII/Hu/GB/2010/GII.P4_GII.4_NewOrleans2009/London48, or if only the capsid sequence is known: norovirus GI/Hu/AU/2012/GII.4 Sydney/Melbourne456.

The vast diversity of strains is ascribed both to the accumulation of point mutations associated with error-prone RNA replication and to recombination between two related viruses. Recombination of noroviruses in the ORF1-ORF2 junction region is a frequent event, and some genotypes seem to be more susceptible to recombination than others. Thus the nomenclature of new norovirus genotypes and variants should be coordinated through international norovirus working group.