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, 361 (18), 1776-85

Norovirus Gastroenteritis


Norovirus Gastroenteritis

Roger I Glass et al. N Engl J Med.

Conflict of interest statement

No other potential conflict of interest relevant to this article was reported.


Figure 1
Figure 1. Phylogenetic Analysis of Noroviruses
Noroviruses are a separate genus in the family Caliciviridae and have great diversity of genogroups, genotypes, and subtypes. Genogroups III and V have been identified only in animals. Strain GI.1 was the original Norwalk virus; other classic viruses named for the locations of outbreaks they caused are shown; strain GII.4 has become the predominant strain in the United States and throughout the world. This multiple alignment of 52 calicivirus viral protein (VP) 1 capsid amino acid sequences was performed with the use of Clustalw2 (, and the phylogenetic analyses were performed with programs in the Phylip package, version 3.6. The scale bars represent the unit for the expected number of substitutions per site. Similar analyses that were performed for recent GII.4 norovirus strains show the emergence of strains every 2 to 4 years. Human prototype viruses are listed in black, porcine viruses GII.11, GII.19, and GII.18 are shown in green, bovine viruses are shown in blue, a murine virus is shown in purple, and a lion virus GIV.2 is shown in red. The prototype strains and the sequence accession references used for this analysis are listed in Table 1 in the Supplementary Appendix.
Figure 2
Figure 2. Structure of Norwalk Virus Capsid and Genome
The top left panel shows the icosahedral capsid structure (showing only the backbone atoms) of Norwalk virus formed by 180 molecules (90 dimers) of the capsid viral protein 1 (VP1), color-coded to show the three domains illustrated in the ribbon representation of the VP1 dimer extracted from the capsid structure (top right panel). The terminals of the capsid dimers are shown, and the region of binding to histo-blood antigen carbohydrate is shown in the dashed box. The bottom panel illustrates virus particles observed on transmission electron microscopy. Particles lacking the genome have dark interiors caused by penetration of the negative stain. The Norwalk virus genome is 7654 nucleotides of positive (+)-sense, single-stranded RNA. A viral protein called VPg is covalently attached to the 5′ end of the RNA, and a polyA tail is at the 3′ end. The incoming genomic RNA functions as a messenger RNA, and it codes for three open reading frames (ORFs). ORF1 is translated as a polyprotein that is cleaved by the virus-encoded protease (Pro) to produce six proteins: p48, nucleoside triphosphatase, p22, VPg, Pro (protease) and Pol (RNA-dependent RNA polymerase). These proteins function in the replication process to copy the (+)-sense genomic RNA into a (−)-sense copy that is used as a template to produce a (+)-sense subgenomic RNA. The subgenomic RNA is translated to produce the major capsid protein (VP1) and a few molecules of a second capsid protein (VP2) that can self-assemble into viruslike particles when these two proteins are expressed alone., P denotes protruding domain, and S shell domain; (A)n indicates that the 3′ end of the RNA is polyadenylated.
Figure 3
Figure 3. Outbreaks of Noroviruses in the United States, 1994 to 2006, According to Genotype and Genogroup
The original Norwalk virus strain, GI.1, is rarely present, whereas GII.4 has become the pandemic strain. The increase in outbreaks after 1996 reflects the application of new polymerase-chain-reaction diagnostics and not an absolute increase in the number of outbreaks that occurred.

Comment in

  • Norovirus gastroenteritis.
    Cremon C, De Giorgio R, Barbara G. Cremon C, et al. N Engl J Med. 2010 Feb 11;362(6):557; author reply 557-8. doi: 10.1056/NEJMc0911723. N Engl J Med. 2010. PMID: 20147725 No abstract available.

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