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Rapid evolution of pandemic noroviruses of the GII.4 lineage.

ABSTRACT: Over the last fifteen years there have been five pandemics of norovirus (NoV) associated gastroenteritis, and the period of stasis between each pandemic has been progressively shortening. NoV is classified into five genogroups, which can be further classified into 25 or more different human NoV genotypes; however, only one, genogroup II genotype 4 (GII.4), is associated with pandemics. Hence, GII.4 viruses have both a higher frequency in the host population and greater epidemiological fitness. The aim of this study was to investigate if the accuracy and rate of replication are contributing to the increased epidemiological fitness of the GII.4 strains. The replication and mutation rates were determined using in vitro RNA dependent RNA polymerase (RdRp) assays, and rates of evolution were determined by bioinformatics. GII.4 strains were compared to the second most reported genotype, recombinant GII.b/GII.3, the rarely detected GII.3 and GII.7 and as a control, hepatitis C virus (HCV). The predominant GII.4 strains had a higher mutation rate and rate of evolution compared to the less frequently detected GII.b, GII.3 and GII.7 strains. Furthermore, the GII.4 lineage had on average a 1.7-fold higher rate of evolution within the capsid sequence and a greater number of non-synonymous changes compared to other NoVs, supporting the theory that it is undergoing antigenic drift at a faster rate. Interestingly, the non-synonymous mutations for all three NoV genotypes were localised to common structural residues in the capsid, indicating that these sites are likely to be under immune selection. This study supports the hypothesis that the ability of the virus to generate genetic diversity is vital for viral fitness.

SUBMITTER: Bull RA

PROVIDER: S-EPMC2847951 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

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Rapid evolution of pandemic noroviruses of the GII.4 lineage.

Bull Rowena A RA Eden John-Sebastian JS Rawlinson William D WD White Peter A PA

PLoS pathogens 20100326 3

Over the last fifteen years there have been five pandemics of norovirus (NoV) associated gastroenteritis, and the period of stasis between each pandemic has been progressively shortening. NoV is classified into five genogroups, which can be further classified into 25 or more different human NoV genotypes; however, only one, genogroup II genotype 4 (GII.4), is associated with pandemics. Hence, GII.4 viruses have both a higher frequency in the host population and greater epidemiological fitness. T ...[more]

PMID: 20360972

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Project description:Genogroup II, genotype 4 (GII.4) noroviruses are known to rapidly evolve, with the emergence of a new primary strain every 2 to 4 years as herd immunity to the previously circulating strain is overcome. Because viral genetic diversity is higher in chronic than in acute infection, chronically infected immunocompromised people have been hypothesized to be a potential source for new epidemic GII.4 strains. However, while some capsid protein residues are under positive selection and undergo patterned changes in sequence variation over time, the relationships between genetic variation and antigenic variation remains unknown. Based on previously published GII.4 strains from a chronically infected individual, we synthetically reconstructed virus-like particles (VLPs) representing early and late isolates from a small-bowel transplant patient chronically infected with norovirus, as well as the parental GII.4-2006b strain. We demonstrate that intrahost GII.4 evolution results in the emergence of antigenically distinct strains over time, comparable to the variation noted between the chronologically predominant GII.4 strains GII.4-2006b and GII.4-2009. Our data suggest that in some individuals the evolution that occurs during a chronic norovirus infection overlaps with changing antigenic epitopes that are associated with successive outbreak strains and may select for isolates that are potentially able to escape herd immunity from earlier isolates.Noroviruses are agents of gastrointestinal illness, infecting an estimated 21 million people per year in the United States alone. In healthy individuals, symptomatic infection typically resolves within 24 to 48 h. However, symptoms may persist for years in immunocompromised individuals, and development of successful treatments for these patients is a continuing challenge. This work is relevant to the design of successful norovirus therapeutics for chronically infected patients; provides support for previous assertions that chronically infected individuals may serve as reservoirs for new, antigenically unique emergent strains; and furthers our understanding of genogroup II, genotype 4 (GII.4) norovirus immune-driven molecular evolution.

Dataset Information

Rapid evolution of pandemic noroviruses of the GII.4 lineage.

Publications

Rapid evolution of pandemic noroviruses of the GII.4 lineage.

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