The RNA genome of the prototype norovirus strain, Norwalk virus (shown at the top), is organized into three open reading frames (ORF1, ORF2, and ORF3) that encode the designated nonstructural and structural proteins. Most diagnostic primers used in reverse-transcriptase–polymerase-chain-reaction assay target conserved areas in the RNA-dependent RNA polymerase region (NS7^POL). VP1, the major capsid protein (shown below), is further organized into the N-terminal (N), shell (S), and protruding (P) domains defined by the indicated VP1 amino acid residues. The P2 region of the P domain (blue) is exposed on the surface of the capsid protein and is the site where histo–blood group antigens (HBGAs) (magenta) interact with the virion (dashed box).^,

The bar graph shows the frequency distribution of VP1 norovirus variants, identified through next-generation sequencing, in an immunocompetent host and an immunocompromised host. Each unique variant is represented by a different color. Given the limited color palette, repeated colors represent distinct variants. Low-frequency variants, with an estimated frequency of occurrence below the detection threshold (2%), are shown in gray. Only two variants were detected in the immunocompetent host, and they remained stable throughout the 10 days of infection. No predominant variant was observed in the immunocompromised host. Instead, numerous low-frequency variants coexisted, and their prevalences varied over the course of the infection. Adapted from Bull et al.