Tetteh K K, Loukas A, Tripp C, Maizels R M
Institute of Cell, Animal and Population Biology, University of Edinburgh, Edinburgh EH9 3JT, Scotland, United Kingdom.
Infect Immun. 1999 Sep;67(9):4771-9. doi: 10.1128/IAI.67.9.4771-4779.1999.
Larvae of Toxocara canis, a nematode parasite of dogs, infect humans, causing visceral and ocular larva migrans. In noncanid hosts, larvae neither grow nor differentiate but endure in a state of arrested development. Reasoning that parasite protein production is orientated to immune evasion, we undertook a random sequencing project from a larval cDNA library to characterize the most highly expressed transcripts. In all, 266 clones were sequenced, most from both 3' and 5' ends, and similarity searches against GenBank protein and dbEST nucleotide databases were conducted. Cluster analyses showed that 128 distinct gene products had been found, all but 3 of which represented newly identified genes. Ninety-five genes were represented by a single clone, but seven transcripts were present at high frequencies, each composing >2% of all clones sequenced. These high-abundance transcripts include a mucin and a C-type lectin, which are both major excretory-secretory antigens released by parasites. Four highly expressed novel gene transcripts, termed ant (abundant novel transcript) genes, were found. Together, these four genes comprised 18% of all cDNA clones isolated, but no similar sequences occur in the Caenorhabditis elegans genome. While the coding regions of the four genes are dissimilar, their 3' untranslated tracts have significant homology in nucleotide sequence. The discovery of these abundant, parasite-specific genes of newly identified lectins and mucins, as well as a range of conserved and novel proteins, provides defined candidates for future analysis of the molecular basis of immune evasion by T. canis.
犬弓首蛔虫是一种寄生于犬类的线虫寄生虫,其幼虫可感染人类,引发内脏幼虫移行症和眼幼虫移行症。在非犬科宿主中,幼虫既不生长也不分化,而是处于发育停滞状态。鉴于寄生虫蛋白质的产生与免疫逃避有关,我们从幼虫cDNA文库开展了一个随机测序项目,以鉴定表达量最高的转录本。总共对266个克隆进行了测序,大多数克隆的3'端和5'端都进行了测序,并与GenBank蛋白质数据库和dbEST核苷酸数据库进行了相似性搜索。聚类分析表明,共发现了128种不同的基因产物,其中除3种外均代表新鉴定的基因。95个基因仅由一个克隆代表,但有7种转录本高频出现,每种转录本占所有测序克隆的2%以上。这些高丰度转录本包括一种粘蛋白和一种C型凝集素,它们都是寄生虫释放的主要排泄-分泌抗原。还发现了4种高度表达的新型基因转录本,称为ant(丰富的新型转录本)基因。这4个基因共占所有分离的cDNA克隆的18%,但在秀丽隐杆线虫基因组中未发现相似序列。虽然这4个基因的编码区不同,但其3'非翻译区在核苷酸序列上具有显著的同源性。这些丰富的、寄生虫特异性的新鉴定凝集素和粘蛋白基因以及一系列保守和新型蛋白质的发现,为未来分析犬弓首蛔虫免疫逃避的分子基础提供了明确的候选对象。