Epigenetic silencing of Plasmodium falciparum genes linked to erythrocyte invasion.
Epigenetic silencing of Plasmodium falciparum genes linked to erythrocyte invasion.
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DOI：
10.1371/journal.ppat.0030107
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发表时间：
2007-08-03
期刊：
影响因子：
6.7
通讯作者：
Holder AA
中科院分区：
文献类型：
--
作者：
Cortés A;Carret C;Kaneko O;Yim Lim BY;Ivens A;Holder AA
恶性疟原虫裂殖子侵入红细胞的过程涉及多个步骤，包括在寄生虫和宿主细胞之间形成移动连接，并且其特征在于所涉及的许多受体-配体相互作用的冗余。与红细胞受体相互作用或参与其他入侵步骤的几种寄生虫蛋白质由四到七个成员的小亚端粒定位基因家族编码。我们在这里报告的EBA，rhoph 1/CLAG，ACBP和PFRh多基因家族的成员存在于一个活跃或沉默的状态。在rhoph 1/clag家族的两个成员clag3.1和clag3.2的情况下，表达是相互排斥的。沉默是克隆传播的，发生在没有可检测的DNA改变的情况下，这表明它是表观遗传的。这在EBA-140中得到了证实。我们的数据表明，疟原虫中的变体或互斥表达和表观遗传沉默并不是var等基因所独有的，var编码的蛋白质被出口到红细胞表面，但也发生在宿主细胞入侵中所涉及的基因。入侵相关配体的克隆变体表达增加了寄生虫适应人类宿主的灵活性。 恶性疟原虫是造成最严重的人类疟疾的原因。入侵宿主红细胞是这种寄生虫复杂生命周期的重要步骤。在这个过程中涉及的许多相互作用中存在冗余，因此寄生虫可以使用不同的受体-配体相互作用来入侵。在这里，我们证明了寄生虫可以关闭一些介导红细胞入侵的蛋白质的表达。通过使用一种称为表观遗传沉默的机制，可以在不改变寄生虫遗传信息的情况下关闭表达。这比遗传变化灵活得多，并且允许快速、可逆的适应。打开或关闭这些蛋白质的表达并不影响寄生虫入侵正常或修饰红细胞的能力，这表明寄生虫可能利用这些基因的变异表达来逃避宿主的免疫反应。参与红细胞侵入的寄生虫蛋白是重要的疫苗候选物。确定哪些蛋白质可以被关闭是很重要的，因为基于寄生虫的单一抗原的疫苗可以被关闭而不影响其生长，这几乎没有机会诱导保护性免疫。
The process of erythrocyte invasion by merozoites of Plasmodium falciparum involves multiple steps, including the formation of a moving junction between parasite and host cell, and it is characterised by the redundancy of many of the receptor–ligand interactions involved. Several parasite proteins that interact with erythrocyte receptors or participate in other steps of invasion are encoded by small subtelomerically located gene families of four to seven members. We report here that members of the eba, rhoph1/clag, acbp, and pfRh multigene families exist in either an active or a silenced state. In the case of two members of the rhoph1/clag family, clag3.1 and clag3.2, expression was mutually exclusive. Silencing was clonally transmitted and occurred in the absence of detectable DNA alterations, suggesting that it is epigenetic. This was demonstrated for eba-140. Our data demonstrate that variant or mutually exclusive expression and epigenetic silencing in Plasmodium are not unique to genes such as var, which encode proteins that are exported to the surface of the erythrocyte, but also occur for genes involved in host cell invasion. Clonal variant expression of invasion-related ligands increases the flexibility of the parasite to adapt to its human host. Plasmodium falciparum is responsible for the most severe forms of human malaria. Invasion of host erythrocytes is an essential step of the complex life cycle of this parasite. There is redundancy in many of the interactions involved in this process, such that the parasite can use different sets of receptor–ligand interactions to invade. Here, we demonstrate that the parasite can turn off the expression of some of the proteins that mediate invasion of erythrocytes. Expression can be turned off without alterations in the genetic information of the parasite by using a mechanism known as epigenetic silencing. This is far more flexible than genetic changes, and permits fast, reversible adaptation. Turning on or off the expression of these proteins did not affect the capacity of the parasite to invade normal or modified red cells, which suggests that the variant expression of these genes may be used by the parasite to escape immune responses from the host. Parasite proteins that participate in erythrocyte invasion are important vaccine candidates. Determining which proteins can be turned off is important because vaccines based on single antigens of the parasite that can be turned off without affecting its growth would have little chance of inducing protective immunity.
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影响因子：
9.8
作者：
Bozdech, Zbynek;Llinas, Manuel;Pulliam, Brian Lee;Wong, Edith D;Zhu, Jingchun;DeRisi, Joseph L
通讯作者：
DeRisi, Joseph L
影响因子：
3.1
作者：
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通讯作者：
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影响因子：
16
作者：
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通讯作者：
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影响因子：
9.4
作者：
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通讯作者：
Beeson, James G.
影响因子：
11.4
作者：
Scherf, A;Hernandez-Rivas, R;Lanzer, M
通讯作者：
Lanzer, M