Heterochromatin Protein 1 Secures Survival and Transmission of Malaria Parasites
Heterochromatin Protein 1 Secures Survival and Transmission of Malaria Parasites
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DOI：
10.1016/j.chom.2014.07.004
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发表时间：
2014-08-13
影响因子：
30.3
通讯作者：
Voss, Till S.
中科院分区：
文献类型：
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作者：
Brancucci, Nicolas M. B.;Bertschi, Nicole L.;Voss, Till S.
表面抗原的克隆变体表达允许疟疾寄生虫恶性疟原虫在血液阶段感染期间逃避免疫识别并确保疟疾传播。我们证明，异染色质蛋白1（HP 1），遗传基因沉默的进化保守的调节器，控制许多恶性疟原虫毒力基因的表达，以及分化成传播给蚊子的有性形式。恶性疟原虫HP 1（PfHP 1）的条件性缺失可防止血液期寄生虫的有丝分裂增殖，并破坏主要毒力因子PfEMP 1的互斥表达和抗原变异。此外，PfAP 2-G，配子体转换所需的转录因子PfHP 1依赖性调节，控制从无性增殖到性分化的开关，提供了深入了解配子体承诺的表观遗传机制。这些发现表明PfHP 1主要参与恶性疟原虫的克隆变异基因表达和性分化，并对开发抗疟疾的抗病和传播阻断干预措施具有重要意义。
Clonally variant expression of surface antigens allows the malaria parasite Plasmodium falciparum to evade immune recognition during blood stage infection and secure malaria transmission. We demonstrate that heterochromatin protein 1 (HP1), an evolutionary conserved regulator of heritable gene silencing, controls expression of numerous P. falciparum virulence genes as well as differentiation into the sexual forms that transmit to mosquitoes. Conditional depletion of P. falciparum HP1 (PfHP1) prevents mitotic proliferation of blood stage parasites and disrupts mutually exclusive expression and antigenic variation of the major virulence factor PfEMP1. Additionally, PfHP1-dependent regulation of PfAP2-G, a transcription factor required for gametocyte conversion, controls the switch from asexual proliferation to sexual differentiation, providing insight into the epigenetic mechanisms underlying gametocyte commitment. These findings show that PfHP1 is centrally involved in clonally variant gene expression and sexual differentiation in P. falciparum and have major implications for developing antidisease and transmission-blocking interventions against malaria.