Association between expression of the H histo-blood group antigen, alpha1,2fucosyltransferases polymorphism of wild rabbits, and sensitivity to rabbit hemorrhagic disease virus

RHDV (rabbit hemorrhagic disease virus) is a highly virulentcalicivirus that has become a major cause of mortality in wildrabbit populations (Oryctolagus cuniculus). It binds to thehisto-blood group antigen (HBGA) H type 2 which requires an1,2fucosyltransferase for its synthesis. In rabbit, three 1,2fucosyltransferasesgenes are known, Fut1, Fut2, and Sec1. Nonfunctional allelesat any of these loci could potentially confer resistance toRHDV, similar to human FUT2 alleles that determine the nonsecretorphenotype and resistance to infection by various NoV strains.In this study, we looked for the presence of H type 2 on buccalepithelial cells of wild rabbits from two geographic areas underRHDV pressure and from one RHDV-free area. Some animals withdiminished H type 2 expression were found in the three populations(nonsecretor-like phenotype). Their frequency markedly increasedaccording to the RHDV impact, suggesting that outbreaks selectedsurvivors with low expression of the virus ligand. Polymorphismsof the Fut1, Fut2, and Sec1 coding regions were determined amonganimals that either died or survived outbreaks. The Fut2 andSec1 genes presented a high polymorphism and the frequency ofone Sec1 allele was significantly elevated, over 6-fold, amongsurvivors. Sec1 enzyme variants showed either moderate, low,or undetectable catalytic activity, whereas all variant Fut2enzymes showed strong catalytic activity. This functional analysisof the enzymes encoded by each Fut2 and Sec1 allele suggeststhat the association between one Sec1 allele and survival mightbe explained by a deficit of 1,2fucosyltransferase expressionrather than by impaired catalytic activity.