Genetic Analysis of the Capsid Gene of Genotype GII.2 Noroviruses

Abstract

Noroviruses (NoVs) are considered to be a major cause of acute nonbacterial gastroenteritis in humans. The NoV genus is genetically diverse, and genotype GII.4 has been most commonly identified worldwide in recent years. In this study we analyzed the complete capsid gene of NoV strains belonging to the less prevalent genotype GII.2. We compared a total of 36 complete capsid sequences of GII.2 sequences obtained from the GenBank (n ‫؍‬ 5) and from outbreaks or sporadic cases that occurred in The Netherlands (n ‫؍‬ 10) and in Osaka City, Japan (n ‫؍‬ 21), between 1976 and 2005. Alignment of all capsid sequences did not show fixation of amino acid substitutions over time as an indication for genetic drift. In contrast, when strains previously recognized as recombinants were excluded from the alignment, genetic drift was observed. Substitutions were found at five informative sites (two in the P1 subdomain and three in the P2 subdomain), segregating strains into five genetic groups (1994 to 1997, 1999 Noroviruses (NoVs) are an important cause of acute nonbacterial gastroenteritis in adults and children worldwide (13). NoVs are members of the family Caliciviridae, having a positive-sense single-stranded RNA genome. Their genome is organized into three open reading frames (ORFs). ORF1 encodes nonstructural proteins including the RNA-dependent RNA polymerase (RdRp), ORF2 encodes a major structural capsid protein including a shell (S) domain and a protruding (P) domain, and ORF3 encodes a minor structural protein (13,18,41). The S domain forms the inner part (shell) of the viral capsid, and the P domain forms the arch-like structures that protrude from the virion. The P domain is further divided into P1 and P2 subdomains that correspond to the sides and the top of the arch-like capsomeres, respectively (13, 31).Based on the genetic analysis of the RdRp and capsid regions, human NoVs can be divided into three genogroups (Gs), GI, GII, and GIV (2, 14, 39), which further segregate into distinct lineages called genotypes (2,20,36,37). Recently, Kageyama et al. (20) proposed that at least 31 genotypes could be distinguished within GI and GII. The GII.4 genotype, which is represented by the Lordsdale/93/UK strain, has been the most commonly identified genotype worldwide in recent years. Genetic characterization of strains belonging to this genotype have shown a sequence of variants that have arisen over time, suggesting that rapid genetic evolution of GII.4 NoVs may in part explain their successful spread and impact on people of all ages (5,9,27,29,30,33,40).Viruses belonging to other NoV genotypes are found less consistently, causing sporadic outbreaks or temporary epidemics in a limited geographic region or time period (5,17,23,26). As a result, far less is known about the population structure of these variants (28). The genetic analysis of other genotype NoVs excluding GII.4 will improve our understanding of genetic evolution and its relevance for the epidemiology of NoVs.During the spring of 2004, an epidemic of GII.2 N...

Heterotypic Humoral and Cellular Immune Responses following Norwalk Virus Infection

“…It appears that the novel strains were defined by targeted variation at select residues within the capsid sequence (40). This variation primarily occurred in the surface-exposed P2 subdomain, suggesting that heterogeneity in the GII.2 strains was mediated by an immune response-driven evolution (40). In addition, similar studies with the GII.3 and GII.4 genotypes show evidence of immune response-driven evolution (12,54).…”

“…For example, a recent bioinformatics study of GII.2 strains suggested that this genotype may be evolving new strains in a time-ordered manner over a 12-year period. It appears that the novel strains were defined by targeted variation at select residues within the capsid sequence (40). This variation primarily occurred in the surface-exposed P2 subdomain, suggesting that heterogeneity in the GII.2 strains was mediated by an immune response-driven evolution (40).…”

Norovirus

“…In addition, mutations and recombination events involving P2 can significantly affect antigen properties and interactions with HBGAs (334). GII.4 strains, in particular, are undergoing rapid evolution that affects receptor binding by changes in surface-exposed P2 and antigenic expression, resulting in the emergence of new epidemic strains of the virus (25, [335][336][337][338][339][340]. In contrast, there has been only limited evolution of GI viruses over the last 4 decades (334).…”

Using Molecular Epidemiology To Trace Transmission of Nosocomial Norovirus Infection

“…Noroviruses have a positive-sense RNA genome with an average length of 7.5 kb (4,8). Noroviruses are genetically highly variable and are classified into 5 genogroups (GI, GII, GIII, GIV, and GV), 3 of which are found in humans (12,24).…”