Single amino acid substitution in Plasmodium yoelii erythrocyte ligand determines its localization and controls parasite virulence
Single amino acid substitution in Plasmodium yoelii erythrocyte ligand determines its localization and controls parasite virulence
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DOI：
10.1073/pnas.0811313106
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发表时间：
2009-04-28
影响因子：
11.1
通讯作者：
Torii, Motomi
中科院分区：
文献类型：
--
作者：
Otsuki, Hitoshi;Kaneko, Osamu;Torii, Motomi
啮齿动物疟疾寄生虫约利疟原虫（Plasmodium yoelii）的主要毒力决定因素自20世纪70年代发现致死性疟原虫以来一直未得到解决。由于这种寄生虫的毒力与入侵不同类型红细胞的能力相关，因此我们评估了寄生虫红细胞结合配体PyEBL的潜在作用。我们发现在致死性和非致死性寄生虫系之间负责细胞内运输的结构域上有1个氨基酸的替换，此外，PyEBL的细胞内定位在这些系之间是不同的。基因修饰表明，这种替代不仅导致了PyEBL的定位，而且导致了寄生虫对红细胞型的入侵偏好以及随后在小鼠中的毒力。这种以前未被认识到的改变入侵表型的机制表明，疟原虫配体的细微改变可以显著影响宿主-病原体相互作用和疟疾毒力。
The major virulence determinant of the rodent malaria parasite, Plasmodium yoelii, has remained unresolved since the discovery of the lethal line in the 1970s. Because virulence in this parasite correlates with the ability to invade different types of erythrocytes, we evaluated the potential role of the parasite erythrocyte binding ligand, PyEBL. We found 1 amino acid substitution in a domain responsible for intracellular trafficking between the lethal and nonlethal parasite lines and, furthermore, that the intracellular localization of PyEBL was distinct between these lines. Genetic modification showed that this substitution was responsible not only for PyEBL localization but also the erythrocyte-type invasion preference of the parasite and subsequently its virulence in mice. This previously unrecognized mechanism for altering an invasion phenotype indicates that subtle alterations of a malaria parasite ligand can dramatically affect host-pathogen interactions and malaria virulence.