Heterochromatin plays a central role in the process of immune evasion, pathogenesis, and transmission of the malaria parasite Plasmodium falciparum during blood stage infection. Here, we use ChIP sequencing to demonstrate that sporozoites from mosquito salivary glands expand heterochromatin at subtelomeric regions to silence blood-stage-specific genes. Our data also revealed that heterochromatin enrichment is predictive of the transcription status of clonally variant genes members that mediate cytoadhesion in blood stage parasites. A specific member (here called NF54var^sporo) of the var gene family remains euchromatic, and the resultant PfEMP1 (NF54_SpzPfEMP1) is expressed at the sporozoite surface. NF54_SpzPfEMP1-specific antibodies efficiently block hepatocyte infection in a strain-specific manner. Furthermore, human volunteers immunized with infective sporozoites developed antibodies against NF54_SpzPfEMP1. Overall, we show that the epigenetic signature of var genes is reset in mosquito stages. Moreover, the identification of a strain-specific sporozoite PfEMP1 is highly relevant for vaccine design based on sporozoites.

中文翻译：

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特定的PfEMP1在恶性疟原虫子孢子中表达，并在肝细胞感染中起作用。

异染色质在血液阶段感染过程中的免疫逃逸，发病机理以及疟原虫恶性疟原虫的传播过程中起着核心作用。在这里，我们使用ChIP测序来证明来自蚊唾液腺的子孢子在亚端粒区域扩展异染色质，以沉默特定的血液阶段基因。我们的数据还显示，异染色质的富集可预测介导血液阶段寄生虫中细胞粘附的克隆变异基因成员的转录状态。特定成员（这里称为NF54var^孢粉）var基因家族的）保持常态，并且所得的PfEMP1（NF54_SpzPfEMP1）在子孢子表面表达。NF54_SpzPfEMP1特异性抗体以菌株特异性方式有效阻断肝细胞感染。此外，用感染子孢子免疫的人类志愿者开发了针对NF54_SpzPfEMP1的抗体。总体而言，我们表明var基因的表观遗传学特征在蚊子阶段被重置。而且，菌株特异性子孢子PfEMP1的鉴定与基于子孢子的疫苗设计高度相关。