ROP18 is a key factor responsible for virulence difference between Toxoplasma gondii and Neospora caninum.

ROP18 is a key factor responsible for virulence difference between Toxoplasma gondii and Neospora caninum.
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ROP18是弓形虫与犬新孢子虫毒力差异的关键因素

DOI:
10.1371/journal.pone.0099744
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Liu Q
Liu Q
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Lei T;Wang H;Liu J;Nan H;Liu Q

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刚地弓形虫(T. gondii)和犬新孢子虫(N. caninum)都是专性细胞内原生动物寄生虫,具有许多共同的形态和生物学特征。尽管有这些相似之处,这两种寄生虫在小鼠体内的毒力差异很大,但两种寄生虫之间毒力差异的因素仍然未知。一种名为弓形虫蛋白18 (ROP18)的分泌丝氨酸-苏氨酸激酶在不同弓形虫克隆谱系的毒力差异中起着至关重要的作用。有趣的是,我们在之前的研究中发现犬链球菌Nc1株的ROP18 (NcROP18)是一个假基因,因为该序列中有几个中断的停止密码子。我们认为弓形虫和犬奈虫的毒力差异是由ROP18基因的差异引起的。我们通过转染弓形虫RH株的TgROP18构建了转基因犬N. Nc1染色。表型和毒力分析结果表明,TgROP18在犬棘球蚴中的表达不影响犬棘球蚴的运动能力和细胞侵袭能力,但显著增加了小鼠胞内寄生虫的增殖和毒力。免疫相关GTPase (IRG)磷酸化实验表明,转基因Nc1-TgROP18能够像弓形虫一样磷酸化IRG。本研究表明,ROP18在密切相关的弓形虫和犬奈虫的毒力中起着至关重要的作用,它确实是造成弓形虫和犬奈虫毒力差异的关键因素。
Toxoplasma gondii (T. gondii) and Neospora caninum (N. caninum) are both obligate intracellular protozoan parasites and share many common morphological and biological features. Despite these similarities the two parasites differ dramatically in virulence in mice, but the factors involved in virulence differences between the two parasites remain unknown. A secreted serine-threonine kinase called rhoptry protein 18 (ROP18) was identified to play a crucial role on virulence differences among different T. gondii clonal lineages. Intriguingly, we found that ROP18 in Nc1 strain of N. caninum (NcROP18) is a pseudogene due to several interrupting stop codons in the sequence in our previous studies. We assume that the difference of ROP18 leads to virulence difference between T. gondii and N. caninum. We constructed a transgenic N. caninum Nc1 stain by transfecting the TgROP18 from the T. gondii RH strain. Phenotype and virulence assays showed that the expression of TgROP18 in N. caninum did not affect the motility and cell invasion, but resulted in a significant increase in intracellular parasite proliferation and virulence in mice. Immunity-Related GTPase (IRG) phosphorylation assay showed that the transgenic parasite Nc1-TgROP18 was able to phosphorylate IRGs as T. gondii did. The present study indicated that the ROP18 plays a crucial role in virulence of the closely related parasites T. gondii and N. caninum and it is indeed a key factor responsible for the virulence difference between T. gondii and N. caninum.
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