The Plasmodium liver-specific protein 2 (LISP2) is an early marker of liver stage development
The Plasmodium liver-specific protein 2 (LISP2) is an early marker of liver stage development
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DOI：
10.7554/elife.43362
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发表时间：
2019-05-16
期刊：
影响因子：
7.7
通讯作者：
Diagana, Thierry Tidiane
中科院分区：
文献类型：
--
作者：
Gupta, Devendra Kumar;Dembele, Laurent;Diagana, Thierry Tidiane
间日疟原虫催眠子在肝脏中持续存在，导致疟疾复发，是消除疟疾的一个主要挑战。我们之前的转录组学研究提供了一种新的分子框架，以增强我们对催眠虫生物学的理解（Voorberg-van der Wel A，et al.，2017年）。在这个数据集中，我们确定并表征了肝脏特异性蛋白2（LISP 2）蛋白作为肝脏阶段发育的早期分子标志物。在体外（食蟹猴疟原虫）和体内（间日疟原虫）感染复发性疟疾寄生虫的肝细胞的免疫荧光分析揭示，LISP 2表达区分休眠的催眠子和早期发育的寄生虫。我们进一步证明，预防性药物选择性地杀死所有LISP 2阳性的寄生虫，而LISP 2阴性的催眠虫只对抗复发药物他非诺喹敏感。我们的研究结果提供了新的生物学见解，在启动肝脏阶段的胚胎发育和早期标记物，适用于开发药物发现检测预测抗复发活性。
Plasmodium vivax hypnozoites persist in the liver, cause malaria relapse and represent a major challenge to malaria elimination. Our previous transcriptomic study provided a novel molecular framework to enhance our understanding of the hypnozoite biology (Voorberg-van der Wel A, et al., 2017). In this dataset, we identified and characterized the Liver-Specific Protein 2 (LISP2) protein as an early molecular marker of liver stage development. Immunofluorescence analysis of hepatocytes infected with relapsing malaria parasites, in vitro (P. cynomolgi) and in vivo (P. vivax), reveals that LISP2 expression discriminates between dormant hypnozoites and early developing parasites. We further demonstrate that prophylactic drugs selectively kill all LISP2-positive parasites, while LISP2-negative hypnozoites are only sensitive to anti-relapse drug tafenoquine. Our results provide novel biological insights in the initiation of liver stage schizogony and an early marker suitable for the development of drug discovery assays predictive of anti-relapse activity.