Association between expression of the H histo-blood group antigen, α1,2fucosyltransferases polymorphism of wild rabbits, and sensitivity to rabbit hemorrhagic disease virus
Association between expression of the H histo-blood group antigen, α1,2fucosyltransferases polymorphism of wild rabbits, and sensitivity to rabbit hemorrhagic disease virus
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DOI：
10.1093/glycob/cwn098
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发表时间：
2009-01-01
期刊：
影响因子：
4.3
通讯作者：
Le Pendu, Jacques
中科院分区：
文献类型：
--
作者：
Guillon, Patrice;Ruvoen-Clouet, Nathalie;Le Pendu, Jacques
RHDV（兔出血性疾病病毒）是一种高毒力的杯状病毒，已成为野兔种群（Oryctolagus cuniculus）死亡的主要原因。它与 2 型组织血型抗原 (HBGA) H 结合，其合成需要 α 1,2 岩藻糖基转移酶。在兔子中，已知有 3 个 α1,2 岩藻糖基转移酶基因：Fut1、Fut2 和 Sec1。这些基因座中任何一个的非功能性等位基因都可能赋予 RHDV 抗性，类似于人类 FUT2 等位基因，决定非分泌者表型和对各种 NoV 病毒株感染的抗性。在这项研究中，我们在来自 RHDV 压力下的两个地理区域和一个无 RHDV 区域的野兔颊上皮细胞上寻找 H 2 型的存在。在这三个群体中发现了一些 H 2 型表达减少的动物（非分泌者样表型）。根据 RHDV 的影响，它们的频率显着增加，这表明暴发选择了病毒配体低表达的幸存者。在死亡或幸存的动物中确定了 Fut1、Fut2 和 Sec1 编码区的多态性。 Fut2 和 Sec1 基因呈现出高度多态性，并且幸存者中一个 Sec1 等位基因的频率显着升高，超过 6 倍。 Sec1 酶变体显示出中等、低或不可检测的催化活性，而所有变体 Fut2 酶都显示出很强的催化活性。对每个 Fut2 和 Sec1 等位基因编码的酶的功能分析表明，一个 Sec1 等位基因与生存之间的关联可能是通过 α1,2 岩藻糖基转移酶表达缺陷来解释的，而不是通过催化活性受损来解释的。
RHDV (rabbit hemorrhagic disease virus) is a highly virulent calicivirus that has become a major cause of mortality in wild rabbit populations (Oryctolagus cuniculus). It binds to the histo-blood group antigen (HBGA) H type 2 which requires an alpha 1,2fucosyltransferase for its synthesis. In rabbit, three alpha 1,2fucosyltransferases genes are known, Fut1, Fut2, and Sec1. Nonfunctional alleles at any of these loci could potentially confer resistance to RHDV, similar to human FUT2 alleles that determine the nonsecretor phenotype and resistance to infection by various NoV strains. In this study, we looked for the presence of H type 2 on buccal epithelial cells of wild rabbits from two geographic areas under RHDV pressure and from one RHDV-free area. Some animals with diminished H type 2 expression were found in the three populations (nonsecretor-like phenotype). Their frequency markedly increased according to the RHDV impact, suggesting that outbreaks selected survivors with low expression of the virus ligand. Polymorphisms of the Fut1, Fut2, and Sec1 coding regions were determined among animals that either died or survived outbreaks. The Fut2 and Sec1 genes presented a high polymorphism and the frequency of one Sec1 allele was significantly elevated, over 6-fold, among survivors. Sec1 enzyme variants showed either moderate, low, or undetectable catalytic activity, whereas all variant Fut2 enzymes showed strong catalytic activity. This functional analysis of the enzymes encoded by each Fut2 and Sec1 allele suggests that the association between one Sec1 allele and survival might be explained by a deficit of alpha 1,2fucosyltransferase expression rather than by impaired catalytic activity.