Targeted deletion of SAP1 abolishes the expression of infectivity factors necessary for successful malaria parasite liver infection.
Targeted deletion of SAP1 abolishes the expression of infectivity factors necessary for successful malaria parasite liver infection.
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DOI：
10.1111/j.1365-2958.2008.06271.x
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发表时间：
2008-07
影响因子：
3.6
通讯作者：
Kappe, Stefan H. I.
中科院分区：
文献类型：
--
作者：
Aly, Ahmed S. I.;Mikolajczak, Sebastian A.;Rivera, Hilda Silva;Camargo, Nelly;Jacobs-Lorena, Vanessa;Labaied, Mehdi;Coppens, Isabelle;Kappe, Stefan H. I.
疟疾寄生虫子孢子通过UIS（在感染性子孢子中上调）基因的上调准备传播给哺乳动物宿主。许多UIS基因产物对于肝细胞内小生境的建立是必不可少的。然而，调节肝脏感染性获得相关基因表达的因素尚不清楚。在此，我们表明，一个保守的疟原虫子孢子低复杂性天冬酰胺丰富的蛋白，SAP1（子孢子天冬酰胺丰富的蛋白1），在疟疾寄生虫肝脏感染的重要作用。在啮齿类疟疾寄生虫约氏疟原虫中有针对性地缺失SAP 1产生了突变寄生虫，这些突变寄生虫正常地穿过并侵入肝细胞，但不能在体外和体内启动肝脏阶段的发育。此外，用Pysap1（−）子孢子进行免疫接种可提供针对野生型子孢子感染的持久无菌保护。引人注目的是，SAP 1的缺乏消除了包括UIS 3、UIS 4和P52在内的必需UIS基因的表达，但不消除编码子孢子蛋白CSP和TRAP等的组成型表达基因的表达。SAP 1定位于子孢子的细胞内部而不是细胞核，表明其参与基因表达控制的转录后机制。这些发现表明，SAP 1是必不可少的肝脏感染可能作为一个选择性调节器控制感染相关的寄生虫效应基因的表达。
Malaria parasite sporozoites prepare for transmission to a mammalian host by upregulation of UIS (Upregulated in Infectious Sporozoites) genes. A number of UIS gene products are essential for the establishment of the intrahepatocytic niche. However, the factors that regulate the expression of genes involved in gain of infectivity for the liver are unknown. Herein, we show that a conserved Plasmodium sporozoite low-complexity asparagine-rich protein, SAP1 (Sporozoite Asparagine-rich Protein 1), has an essential role in malaria parasite liver infection. Targeted deletion of SAP1 in the rodent malaria parasite Plasmodium yoelii generated mutant parasites that traverse and invade hepatocytes normally but cannot initiate liver-stage development in vitro and in vivo. Moreover, immunizations with Pysap1(−) sporozoites confer long-lasting sterile protection against wild-type sporozoite infection. Strikingly, lack of SAP1 abolished expression of essential UIS genes including UIS3, UIS4 and P52 but not the constitutively expressed genes encoding, among others, sporozoite proteins CSP and TRAP. SAP1 localization to the cell interior but not the nucleus of sporozoites suggests its involvement in a post-transcriptional mechanism of gene expression control. These findings demonstrate that SAP1 is essential for liver infection possibly by functioning as a selective regulator controlling the expression of infectivity-associated parasite effector genes.
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影响因子：
7
作者：
Coulson, RMR;Hall, N;Ouzounis, CA
通讯作者：
Ouzounis, CA
影响因子：
64.8
作者：
Mueller, AK;Labaied, M;Matuschewski, K
通讯作者：
Matuschewski, K
影响因子：
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Labaied, Mehdi;Harupa, Anke;Kappe, Stefan H. I.
通讯作者：
Kappe, Stefan H. I.
影响因子：
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作者：
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通讯作者：
Rodríguez, A
影响因子：
4
作者：
Bergman, LW;Kaiser, K;Kappe, SHI
通讯作者：
Kappe, SHI