首页> 外文期刊>Infection and immunity >Diversity of Ehrlichia ruminantium Major Antigenic Protein 1-2 in Field Isolates and Infected Sheep
【24h】

Diversity of Ehrlichia ruminantium Major Antigenic Protein 1-2 in Field Isolates and Infected Sheep

机译:野外分离株和感染绵羊中沙眼衣原体主要抗原蛋白1-2的多样性

获取原文
           

摘要

Proteins expressed from the map1 multigene family of Ehrlichia ruminantium are strongly recognized by immune T and B cells from infected animals or from animals that were infected and have recovered from heartwater disease (although still remaining infected carriers). Analogous multigene clusters also encode the immunodominant outer membrane proteins (OMPs) in other ehrlichial species. Recombinant protein analogs of the expressed genes and DNA vaccines based on the multigene clusters have been shown to induce protective immunity, although this was less effective in heterologous challenge situations, where the challenge strain major antigenic protein 1 (MAP1) sequence differed from the vaccine strain MAP1. Recent data for several ehrlichial species show differential expression of the OMPs in mammalian versus tick cell cultures and dominant expression of individual family members in each type of culture system. However, many genes in the clusters appear to be complete and functional and to generate mRNA transcripts. Recent data also suggest that there may be a low level of protein expression from many members of the multigene family, despite primary high-level expression from an individual member. A continuing puzzle, therefore, is the biological roles of the different members of these OMP multigene families. Complete genome sequences are now available for two geographically divergent strains of E. ruminantium (Caribbean and South Africa strains). Comparison of these sequences revealed amino acid sequence diversity in MAP1 (89% identity), which is known to confer protection in a mouse model and to be the multigene family member primarily expressed in mammalian cells. Surprisingly, however, the greatest sequence diversity (79% identity) was in the less-studied map1-2 gene. We investigated here whether this map1-2 diversity was a general feature of E. ruminantium in different cultured African strains and in organisms from infected sheep. Comparison of MAP1-2s revealed amino acid identities of 75 to 100% (mean of 86%), compared to 84 to 100% (mean of 89%) for MAP1s. Interestingly, MAP1-2s varied independently of MAP1s such that E. ruminantium strains with similar MAP1s had diverse MAP1-2s and vice versa. Different MAP1-2s were found in individual infected sheep. Different regions of a protein may be subjected to different evolutionary forces because of recombination and/or selection, which results in those regions not agreeing with a phylogeny deduced from the whole molecule. This appears to be true for both MAP1 and MAP1-2, where statistical likelihood methods detect heterogeneous evolutionary rates for segments of both molecules. Sera from infected cattle recognized a MAP1-2 variable-region peptide in enzyme-linked immunosorbent assay, but less strongly and consistently than a MAP1 peptide (MAP1B). Heterologous protective immunity may depend on recognition of a complex set of varying OMP epitopes.
机译:反刍动物毛虫的 map1 多基因家族表达的蛋白质被感染动物或被感染并已从心脏病中恢复的动物的免疫T和B细胞强烈识别(尽管仍然是感染的携带者)。相似的多基因簇还编码其他蛋白质物种中的免疫显性外膜蛋白(OMP)。已显示出表达的基因的重组蛋白类似物和基于多基因簇的DNA疫苗可诱导保护性免疫,尽管在异源攻击情况下这种保护效果较差,在这种情况下,攻击菌株主要抗原蛋白1(MAP1)序列与疫苗菌株不同MAP1。几种大肠杆菌的最新数据显示,在哺乳动物和壁虱细胞培养物中,OMP的差异表达以及每种培养系统中单个家族成员的显性表达。但是,簇中的许多基因似乎是完整的和有功能的,并能产生mRNA转录本。最近的数据还表明,尽管来自单个成员的主要高水平表达,多基因家族许多成员的蛋白表达水平可能较低。因此,一个持续的难题是这些OMP多基因家族的不同成员的生物学作用。现在,完整的基因组序列可用于两个在地理上不同的Eem菌株。反刍动物(加勒比和南非菌株)。这些序列的比较揭示了MAP1中的氨基酸序列多样性(89%的同一性),已知它在小鼠模型中具有保护作用,并且是主要在哺乳动物细胞中表达的多基因家族成员。令人惊讶的是,最大的序列多样性(79%的同一性)是在研究较少的 map1-2 基因中。我们在这里调查了 map1-2 的多样性是否是 E的一般特征。反刍动物在不同的非洲养殖菌株中以及感染绵羊的生物中MAP1-2s的比较显示氨基酸同一性为75%至100%(平均86%),而MAP1s为84%至100%(平均89%)。有趣的是,MAP1-2s独立于MAP1s而变化,以致 E。具有相似的MAP1的反刍动物菌株具有不同的MAP1-2,反之亦然。在个别感染绵羊中发现了不同的MAP1-2s。由于重组和/或选择,蛋白质的不同区域可能会受到不同的进化力,这导致那些区域与从整个分子推导的系统发育不一致。这对于MAP1和MAP1-2似乎都是正确的,其中统计似然方法检测两个分子片段的异质进化速率。来自被感染牛的血清在酶联免疫吸附测定中识别出MAP1-2可变区肽,但强度和一致性不如MAP1肽(MAP1B)。异源保护性免疫可能取决于对一组复杂的不同OMP表位的识别。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号