Histo-blood group antigens act as attachment factors of rabbit hemorrhagic disease virus infection in a virus strain-dependent manner.
Histo-blood group antigens act as attachment factors of rabbit hemorrhagic disease virus infection in a virus strain-dependent manner.
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DOI：
10.1371/journal.ppat.1002188
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发表时间：
2011-08
期刊：
影响因子：
6.7
通讯作者：
Le Pendu J
中科院分区：
文献类型：
--
作者：
Nyström K;Le Gall-Reculé G;Grassi P;Abrantes J;Ruvoën-Clouet N;Le Moullac-Vaidye B;Lopes AM;Esteves PJ;Strive T;Marchandeau S;Dell A;Haslam SM;Le Pendu J
兔出血症病毒（RHDV）是兔病毒属的杯状病毒，引起兔出血症（RHD），在感染后48至72小时内杀死兔，死亡率高达50- 90%。杯状病毒，包括诺如病毒和RHDV，已显示结合组织血型抗原（HBGA），并且已发现在上皮中缺乏ABH抗原的人非分泌型个体对诺如病毒感染具有抗性。RHDV病毒样颗粒先前已显示结合H 2型和A型抗原。在这项研究中，我们提出了一个全面的评估不同的RHDV分离株的HBGAs的菌株特异性结合模式。我们通过质谱和A、B和H 2型表达的相对定量来表征野生兔和家兔十二指肠中HBGA的表达。对一系列RHDV毒株与合成糖和人红细胞以及兔十二指肠（病毒进入的可能胃肠道部位）的结合进行了详细分析。HBGA表位的酶切证实了结合特异性。观察到以菌株依赖性方式与血型B、A和H 2型表位结合，其中对A、B或H表位的特异性略有差异，使得RHDV菌株优先识别不同的动物亚组。与最早描述的RHDV爆发相关的菌株不能结合A，而所有其他基因型都获得了A结合。在实验感染研究中，缺乏正确HBGA配体的兔子在低攻击剂量下对致死性RHDV感染具有抗性。同样，野生种群中爆发的幸存者表现出弱结合表型的频率增加，表明宿主抗性的选择取决于种群中流行的菌株。因此，HBGAs作为附着因子促进感染，而其表达的多态性可能有助于在群体水平上产生对RHDV的遗传抗性。兔出血症病毒（RHDV），发现晚于1984年，已蔓延到世界大部分地区，威胁兔种群和其他物种依赖兔子在许多欧洲国家。死亡率高达90%，兔子在感染后48至72小时被杀死。被称为诺如病毒的相关病毒以依赖于组织血型抗原（HBGA）的表达的方式感染人类，所述组织血型抗原不仅在红细胞上表达，而且在上皮细胞、唾液和肠道的粘蛋白上表达。RHDV也与HBGA结合，在本报告中，我们描述了RHDV所有基因组菌株与不同HBGA的结合。我们还证明了HBGAs在挑战实验中作为附着因子发挥作用。由于参与HBGA合成的基因多态性将兔子种群分为不同的亚群，我们发现在从RHDV毁灭性爆发中恢复的种群中选择了低结合力的野兔亚群。这是第一次证明RHDV株的不同HBGA特异性，描述了感染中的功能，并证明了基于HBGA表型的RHDV感染的宿主选择。
Rabbit Hemorrhagic disease virus (RHDV), a calicivirus of the Lagovirus genus, and responsible for rabbit hemorrhagic disease (RHD), kills rabbits between 48 to 72 hours post infection with mortality rates as high as 50–90%. Caliciviruses, including noroviruses and RHDV, have been shown to bind histo-blood group antigens (HBGA) and human non-secretor individuals lacking ABH antigens in epithelia have been found to be resistant to norovirus infection. RHDV virus-like particles have previously been shown to bind the H type 2 and A antigens. In this study we present a comprehensive assessment of the strain-specific binding patterns of different RHDV isolates to HBGAs. We characterized the HBGA expression in the duodenum of wild and domestic rabbits by mass spectrometry and relative quantification of A, B and H type 2 expression. A detailed binding analysis of a range of RHDV strains, to synthetic sugars and human red blood cells, as well as to rabbit duodenum, a likely gastrointestinal site for viral entrance was performed. Enzymatic cleavage of HBGA epitopes confirmed binding specificity. Binding was observed to blood group B, A and H type 2 epitopes in a strain-dependent manner with slight differences in specificity for A, B or H epitopes allowing RHDV strains to preferentially recognize different subgroups of animals. Strains related to the earliest described RHDV outbreak were not able to bind A, whereas all other genotypes have acquired A binding. In an experimental infection study, rabbits lacking the correct HBGA ligands were resistant to lethal RHDV infection at low challenge doses. Similarly, survivors of outbreaks in wild populations showed increased frequency of weak binding phenotypes, indicating selection for host resistance depending on the strain circulating in the population. HBGAs thus act as attachment factors facilitating infection, while their polymorphism of expression could contribute to generate genetic resistance to RHDV at the population level. Rabbit hemorrhagic disease virus (RHDV), detected as late as 1984, has spread to large parts of the world, threatening rabbit populations and other species dependent on rabbits in many European countries. Mortality has been shown to be as high as 90% and rabbits are killed 48 to 72 hours after infection. Related viruses called noroviruses, infect humans in a manner dependent on the expression of histo-blood group antigens (HBGAs), which are not only expressed on red blood cells, but also on epithelial cells, in saliva and on mucins of the intestinal tract. RHDV also binds to HBGA and in this report we characterize binding of strains of all genetic groups of RHDV to different HBGAs. We also demonstrate HBGAs to function as attachment factors in a challenge experiment. As polymorphisms of genes involved in HBGA synthesis divide the rabbit population into different subgroups, we find selection of low-binding subgroups of wild rabbits in populations recovering from devastating outbreaks of RHDV. This is the first demonstration of differential HBGA specificities of RHDV strains, description of function in infection and demonstration of host selection due to RHDV infection based on HBGA phenotype.
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影响因子：
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