Editorial Commentary: Ancestry-Based Differences in Norovirus Susceptibility: Implications for Understanding Global Infection Patterns

Noroviruses infect an estimated 21 million people annually and are a leading cause of acute gastroenteritis in the United States, making them a major health concern [1]. Despite the widespread prevalence of noroviruses, epidemiology of these viruses is poorly understood, even in the United States and European countries with active surveillance efforts. One critical factor that has been widely overlooked is whether geographic and ancestral differences among human populations impact outcomes such as local disease incidence, local norovirus genotype prevalence, and population-wide transmission patterns. Previous work has demonstrated a link between human genetic factors and norovirus susceptibility. Specifically, both histo-blood group antigen (HBGA) expression and secretor status (presence of a functional FUT2 gene) have been shown to alter an individual’s susceptibility to norovirus infection [2, 3]. Although these factors have been recognized as susceptibility markers in individuals for more than a decade, their relationship to population-level norovirus epidemiology has not been characterized. In this issue of Clinical Infectious Diseases, Currier et al report results of a large-scale, multisite study that investigates the relationship between secretor status, norovirus susceptibility, and ancestry. This study takes an important step in exploring secretor status as it relates to ancestry in a pediatric population in the United States. The results of this study demonstrate ancestry-specific differences in norovirus susceptibility related to secretor status, suggesting that what is known about norovirus infection in white populations is not necessarily transferrable to other ethnic groups. To appreciate the global consequences of genetic diversity as it relates to norovirus infection and vaccine design, a better understanding of ancestry-specific genotypes and comprehensive, worldwide norovirus surveillance is necessary. In their report, Currier et al present a well-constructed study utilizing robust control methodologies and novel testing procedures. This is the first norovirus susceptibility study to utilize the Immunochip, which is a high-throughput genotyping chip that allows for the determination of several genetic factors at once [4]. Here, it was used to detect singlenucleotide polymorphisms in the FUT2 locus, genotype the ABO locus, and identify ancestry based on 1723 ancestral informative markers. HBGAs are a diverse family of carbohydrates that are genetically encoded and expressed in saliva and on mucosal surfaces of the human gut. They serve as binding ligands and putative receptors for the >30 different norovirus genotypes. Viral binding to these various HBGAs occurs in a strainspecific manner [5]. Previous work has demonstrated that individuals who express O-type HBGAs are more susceptible to GI.1 norovirus infection than those who express A and B-type HBGAs [2, 3], although, for other genotypes, no association between infection and ABO expression was found [6]. In addition, susceptibility to norovirus is genetically mediated by the presence of a functional FUT2 gene [2], as this enzyme is needed for the synthesis of ABO Received 19 February 2015; accepted 20 February 2015; electronically published 5 March 2015. Correspondence: Kari Debbink, PhD, Department of Internal Medicine, University of Michigan, 5528 MSRB I, 1150 W Medical Center Dr, Ann Arbor, MI 48109-5680 (kdebbink@umich. edu). Clinical Infectious Diseases 2015;60(11):1639–41 © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of thework, in anymedium, provided theoriginalwork is not altered or transformed in anyway, and that thework is properly cited. For commercial re-use, please contact journals.permissions@oup. com. DOI: 10.1093/cid/civ168