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.
Highlights
Norovirus (NoV), a member of the Caliciviridae family, is considered the most common cause of viral gastroenteritis outbreaks in adults worldwide [1]
Our current knowledge of NoV replication and evolution has made it difficult to predict the efficacy of a treatment or longevity of a vaccine, as evidence is emerging that NoV, like many other RNA viruses, exists as a dynamic, rapidly evolving and genetically diverse population [2,3,4]
The results of this study suggest that, like influenza A, the increased incidence of the pandemic GII.4 lineage may be a result of the combined influence of a high mutation, replication and evolution rate which, together culminate in an increased epidemiological fitness for the GII.4 strains
Summary
Norovirus (NoV), a member of the Caliciviridae family, is considered the most common cause of viral gastroenteritis outbreaks in adults worldwide [1]. In the US, NoV has been identified as the cause of over 73% of outbreaks of gastroenteritis [1]. Outbreak NoV strains spread rapidly causing great economic burden on society due to medical and social expenses. Our current knowledge of NoV replication and evolution has made it difficult to predict the efficacy of a treatment or longevity of a vaccine, as evidence is emerging that NoV, like many other RNA viruses, exists as a dynamic, rapidly evolving and genetically diverse population [2,3,4]. In order to develop a successful treatment or control program it is first necessary to understand the mechanisms behind NoV replication and evolution
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
