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恶性疟原虫配子细胞中var基因家族而非stevor基因家族的程序化转录。

Programmed transcription of the var gene family, but not of stevor, in Plasmodium falciparum gametocytes.

作者信息

Sharp Sarah, Lavstsen Thomas, Fivelman Quinton L, Saeed Maha, McRobert Louisa, Templeton Thomas J, Jensen Anja T R, Baker David A, Theander Thor G, Sutherland Colin J

机构信息

Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.

出版信息

Eukaryot Cell. 2006 Aug;5(8):1206-14. doi: 10.1128/EC.00029-06.

Abstract

The var genes encode Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) proteins, a set of highly diverse surface-expressed proteins that mediate adhesion of erythrocytes infected with asexual blood-stage parasites to host endothelium. Switching among expressed PfEMP1 variants in the course of a blood-stage infection is a key component of antigenic variation, and thus immune evasion, by the parasite. The majority of var loci are found in the subtelomeric regions of P. falciparum chromosomes associated with members of other multigene families, including stevor. Both PfEMP1 and STEVOR are expressed in gametocytes, the transmissible parasite stage, but the role of these proteins in the biology of sexual-stage parasites remains unknown. PfEMP1 may continue to mediate antigenic variation in gametocytes, which need to persist in the host for many days before reaching maturity. Using quantitative reverse transcription-PCR and Northern hybridization, we demonstrate that transcription of a defined subset of type C var loci occurs during gametocyte development in vitro. This transcriptional program occurs in gametocytes regardless of the var expression phenotype of their asexual progenitors and therefore is subject to regulatory processes distinct from those that manage antigenic variation in the asexual parasite. In contrast, the same stevor variants are transcribed in both gametocytes and their asexual progenitors. We also provide evidence that for both asexual parasites and gametocytes, var and stevor transcription patterns are not linked to each other.

摘要

var基因编码恶性疟原虫红细胞膜蛋白1(PfEMP1),这是一组高度多样的表面表达蛋白,介导无性血液期寄生虫感染的红细胞与宿主内皮细胞的黏附。在血液期感染过程中,表达的PfEMP1变体之间的转换是寄生虫抗原变异进而免疫逃避的关键组成部分。大多数var基因座位于恶性疟原虫染色体的亚端粒区域,与包括stevor在内的其他多基因家族成员相关。PfEMP1和STEVOR都在配子体(可传播的寄生虫阶段)中表达,但这些蛋白在有性阶段寄生虫生物学中的作用仍然未知。PfEMP1可能在配子体中继续介导抗原变异,配子体需要在宿主中持续存在许多天才能成熟。使用定量逆转录PCR和Northern杂交,我们证明在体外配子体发育过程中,特定C型var基因座子集发生转录。无论其无性祖细胞的var表达表型如何,这种转录程序都在配子体中发生,因此受不同于管理无性寄生虫抗原变异的调控过程的控制。相比之下,相同的stevor变体在配子体及其无性祖细胞中都有转录。我们还提供证据表明,对于无性寄生虫和配子体,var和stevor转录模式彼此不相关。

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