Human host genetics of local populations may drive norovirus evolution and diversity, which may have implications for vaccine development, according to data published in the Journal of Infectious Diseases.

Noroviruses are a leading cause of acute gastroenteritis across the world. The GII strains are associated with roughly 90% of such infection worldwide; of this group, GII.4 is the most prevalent genotype, responsible for 50% to 80% of all norovirus outbreaks. The mechanism of infection with noroviruses occurs via virus binding to histoblood groups on the surface of gastroduodenal epithelial cells, which is facilitated by 2 enzymes. Although some strains of noroviruses do not require the presence of these enzymes to facilitate infection (secretor-dependent), individuals who are secretors are at a markedly increased risk for infection.

Investigators conducted a systematic review of studies reporting norovirus outbreak or sporadic case genotypes and combined the data with results from a separate systematic review on proportions of human secretor status in various countries. Estimates of the association between the magnitude of the population who are secretors and the observation of GII.4 were made using inverse variance-weighted linear regression.

In total, 219 genotype and 112 secretor studies were included, which contained data from 38 countries. The study-level GII.4 percentage of all noroviruses ranged from 0% to 100%, and country secretor percentage ranged from 43.8% to 93.9%. An increase of 0.69% (95% CI, 0.19%-1.18%) in GII.4 for each percentage increase in human secretor proportion was observed after controlling for Human Development Index.

Because these data are based on secondary analysis of previously published work, it is subject to limitations in the designs of the original work. Further, the data used for this study were representative of 38 countries as a result of the availability of both secretor and GII.4 data, and there was an overrepresentation of the Western Pacific region. This raised some concerns about generalizability of the results. The investigators further noted that country-level secretor proportion does not account for any within-country heterogeneity, meaning individual studies on secretor proportion may not be representative of a whole country. The analysis was also unable to consider spatial effects, and human and viral diversity do not conform to country boundaries; these 2 limitations may result in misclassification of secretor status and bias the relationship between secretor status and GII.4 toward the null, potentially underestimating the true relationship.

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The investigators concluded that using the systematic literature review, “a positive population-level relationship was identified between the proportion of human secretor status in a population and predominance of the GII.4 norovirus genotype,” a finding they believe may have implications for vaccination. There remains an important question, however, as to whether populations with a higher proportion of secretors have higher overall incidence of norovirus gastroenteritis. Researchers also recommended that future work aim to identify public health consequences of this co-evolution and its implications on vaccine development.

Reference

Arrouzet CJ, Ellis K, Kambhampati A, Chen Y, Steele M, Lopman B. Population-level human secretor status is associated with genogroup 2 type 4 norovirus predominance [published online January 4, 2020]. J Infect Dis. doi:10.1093/infdis/jiz693