Noroviruses are genetically diverse RNA viruses associated with acute gastroenteritis in mammalian hosts. Phylogenetically, they can be segregated into different genogroups as well as P (polymerase)-groups and further into genotypes and P-types based on amino acid diversity of the complete VP1 gene and nucleotide diversity of the RNA-dependent RNA polymerase (RdRp) region of ORF1, respectively. In recent years, several new noroviruses have been reported that warrant an update of the existing classification scheme. Using previously described 2× standard deviation (sd) criteria to group sequences into separate clusters, we expanded the number of genogroups to 10 (GI-GX) and the number of genotypes to 49 (9 GI, 27 GII, 3 GIII, 2 GIV, 2 GV, 2 GVI and 1 genotype each for GVII, GVIII, GIX [formerly GII.15] and GX). Viruses for which currently only one sequence is available in public databases were classified into tentative new genogroups (GNA1 and GNA2) and genotypes (GII.NA1, GII.NA2 and GIV.NA1) with their definitive assignment awaiting additional related sequences. Based on nucleotide diversity in the RdRp region, noroviruses can be divided into 60 P-types (14 GI, 37 GII, 2 GIII, 1 GIV, 2 GV, 2 GVI, 1 GVII and 1 GX), 2 tentative P-groups and 14 tentative P-types. Future classification and nomenclature updates will be based on complete genome sequences and will be coordinated and disseminated by the international norovirus classification-working group.

The International Committee on Taxonomy of Viruses (ICTV) has recently approved several proposals submitted by the present Caliciviridae Study Group.

Norovirus causes gastroenteritis in immunocompetent and immunocompromised hosts. It is the most common cause of gastroenteritis in U.S. adults seeking emergency department care. Genetic features and emerging treatments are discussed.

Noroviruses are major pathogens associated with acute gastroenteritis worldwide. Their RNA genomes are diverse, with two major genogroups (GI and GII) comprised of at least 28 genotypes associated with human disease. To elucidate mechanisms underlying norovirus diversity and evolution, we used a large-scale genomics approach to analyze human norovirus sequences. Comparison of over 2000 nearly full-length ORF2 sequences representing most of the known GI and GII genotypes infecting humans showed a limited number (≤5) of distinct intra-genotypic variants within each genotype, with the exception of GII.4. The non-GII.4 genotypes were comprised of one or more intra-genotypic variants, with each variant containing strains that differed by only a few residues over several decades (remaining “static”) and that have co-circulated with no clear epidemiologic pattern. In contrast, the GII.4 genotype presented the largest number of variants (>10) that have evolved over time with a clear pattern of periodic variant replacement. To expand our understanding of these two patterns of diversification (“static” versus “evolving”), we analyzed using NGS the nearly full-length norovirus genome in healthy individuals infected with GII.4, GII.6 or GII.17 viruses in different outbreak settings. The GII.4 viruses accumulated mutations rapidly within and between hosts, while the GII.6 and GII.17 viruses remained relatively stable, consistent with their diversification patterns. Further analysis of genetic relationships and natural history patterns identified groupings of certain genotypes into larger related clusters designated here as “immunotypes”. We propose that “immunotypes” and their evolutionary patterns influence the prevalence of a particular norovirus genotype in the human population. Efforts are underway to develop vaccines against norovirus, a leading cause of acute gastroenteritis. The purpose of our study was to understand how norovirus strains within different genotypes evolve and adapt as they are transmitted in the human population. Using large-scale genomics and computational tools developed in our laboratory, we identified two strikingly different evolutionary patterns among norovirus genotypes: “static” and “evolving.” We mined large datasets from infection and outbreak studies in context of these evolutionary patterns and propose a new model for antigenic clustering of norovirus genotypes that could simplify vaccine design.

The mouse macrophage-like cell line RAW264.7, the most commonly used mouse macrophage cell line in medical research, was originally reported to be free of replication-competent murine leukemia virus (MuLV) despite its origin in a tumor induced by Abelson MuLV containing Moloney MuLV as helper virus. As currently available, however, we find that it produces significant levels of ecotropic MuLV with the biologic features of the Moloney isolate and also MuLV of the polytropic or MCF class. Newborn mice developed lymphoma following inoculation with the MuLV mixture expressed by these cells. These findings should be considered in interpretation of increasingly widespread use of these cells for propagation of other viruses, studies of biological responses to virus infection and use in RNA interference and cell signalling studies.

A porcine enteric calicivirus (PEC), strain Cowden in the family Caliciviridae (genus Sapovirus ), can be propagated in a continuous cell line, LLC-PK cells, but only in the presence of an intestinal content fluid filtrate from gnotobiotic pigs. This cell culture system is presently the only in vitro model among caliciviruses that cause gastrointestinal disease, including members of the genera Sapovirus and Norovirus . We report here the identification of bile acids as active factors in intestinal content fluid essential for PEC growth. Bile acids that allowed PEC growth induced an increase in cAMP concentration in LLC-PK cells that was associated with down-regulation of IFN-mediated signal transducer and activator of transcription 1 phosphorylation, a key element in innate immunity. In addition, cAMP/protein kinase A pathway inhibitors, suramin, MDL12330A, or H89 suppressed bile acid-mediated PEC replication. We propose a mechanism for enteric calicivirus growth dependent on bile acids, ubiquitous molecules present in the intestine at the site of the virus replication that involves the protein kinase A cell-signaling pathway and a possible down-regulation of innate immunity.