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Innate Resistance and Susceptibility to Norovirus Infection

2016; Public Library of Science; Volume: 12; Issue: 4 Linguagem: Inglês

10.1371/journal.ppat.1005385

1553-7374

Johan Nordgren, Sumit Sharma, Anita Kambhampati, Ben Lopman, Lennart Svensson,

Respiratory viral infections research

The notion that certain individuals appear more or less susceptible to infections or to specific microbes is not new, but, until recently, it was assumed that clinical outcome of an infection was mainly owing to virulence factors of the microorganism.Relatively little attention has been given to host genetic factors involved in innate or adaptive immunity or expression of pathogen receptors.A remarkable example of susceptibility dependence is the strong Mendelian trait resistance to the most common noroviruses among individuals with a nonsense mutation in chromosome 19 [1].Norovirus is recognized as the leading cause of gastroenteritis worldwide, affecting children and adults alike [2].Noroviruses are highly contagious and genetically diverse RNA viruses, but not all individuals are susceptible to infection to the same norovirus genotypes.Presence of histo-blood group antigens (HBGAs) on gut epithelial surfaces is essential for susceptibility to many norovirus genotypes.The synthesis of these HBGAs, specifically of the ABH and Lewis families, requires the use of several fucosyl and glycosyltransferases encoded by the FUT2, FUT3, and ABH genes.Polymorphisms in these genes vary considerably depending on ethnicity, with a homozygous nonsense mutation (individuals called non-secretors) in the FUT2 gene occurring in approximately 5%-50% of different populations worldwide [3][4][5].Secretor status also affects gut microbiota composition, including HBGA-expressing bacteria and bacteria inducing fucosylation in the gut.These could be intermediary factors that govern norovirus susceptibility [6-9]. Does Secretor Status Mediate Resistance to Norovirus Infection?Noroviruses infecting humans are highly diverse and comprise three genogroups and at least 33 genotypes, which are classified according to nucleotide identities in the major capsid protein gene.The earliest volunteer studies in the 1970s used the first isolated norovirus, the Norwalk virus (genogroup I, genotype 1, GI.1) [10].These early studies hinted that not all individuals were inherently susceptible and, in the last decade, challenge and outbreak studies from several countries have confirmed a genetic component to norovirus susceptibility.Moreover, different norovirus genotypes are clearly associated with different epidemiological and susceptibility patterns.The globally dominant GII.4 viruses exhibit a strong secretor specificity in vivo [1]; furthermore, some data suggest that these viruses may possibly be more clinically severe [11,12].Observational studies in countries such as the United States, Ecuador, Burkina Faso, Vietnam, China, and Nicaragua have consistently identified that non-secretors are highly resistant to GII.4 and that GII.4 variants emerging over time have similar secretor specificity in vivo, although in vitro studies have shown that some GII.4 variants can bind to sugars present in non-secretors [3,[13][14][15][16][17].