Identification of Proteins from Plasmodium falciparum That Are Homologous to Reticulocyte Binding Proteins in Plasmodium vivax

Plasmodium falciparum infections can be fatal, while P. vivax infections usually are not. A possible factor involved in the greater virulence of P. falciparum is that this parasite grows in red blood cells (RBCs) of all maturities whereas P. vivax is restricted to growth in reticulocytes, which represent only approximately 1% of total RBCs in the periphery. Two proteins, expressed at the apical end of the invasive merozoite stage from P. vivax, have been implicated in the targeting of reticulocytes for invasion by this parasite. A search of the P. falciparum genome databases has identified genes that are homologous to the P. vivax rbp-1 and -2 genes. Two of these genes are virtually identical over a large region of the 5′ end but are highly divergent at the 3′ end. They encode high-molecular-mass proteins of >300 kDa that are expressed in late schizonts and localized to the apical end of the merozoite. To test a potential role in merozoite invasion of RBCs, we analyzed the ability of these proteins to bind to mature RBCs and reticulocytes. No binding to mature RBCs or cell preparations enriched for reticulocytes was detected. We identified a parasite clone that lacks the gene for one of these proteins, showing that the gene is not required for normal in vitro growth. Antibodies to these proteins can inhibit merozoite invasion of RBCs.

恶性疟原虫（Plasmodium falciparum）感染可致死，而间日疟原虫（P. vivax）感染通常不会。恶性疟原虫毒力更强的潜在相关因素之一为：该寄生虫可侵染各发育阶段的红细胞（red blood cells, RBCs），而间日疟原虫仅能在网织红细胞（reticulocytes）中增殖；外周血中网织红细胞仅占总红细胞的约1%。间日疟原虫侵袭性裂殖子（merozoite）阶段顶端表达的两种蛋白，被认为参与介导该疟原虫靶向网织红细胞完成侵袭。对恶性疟原虫基因组数据库的检索发现，存在与间日疟原虫rbp-1和rbp-2基因同源的基因。其中两个基因在5'端的大片段区域序列几乎完全一致，但在3'端呈现高度分化。它们编码分子量大于300 kDa的高分子量蛋白，在晚期裂殖体（schizont）中表达，并定位于裂殖子的顶端。为验证这些蛋白在裂殖子侵袭红细胞过程中的潜在作用，我们分析了它们结合成熟红细胞与网织红细胞的能力。实验未检测到这些蛋白与成熟红细胞或富集网织红细胞的细胞制剂的结合。我们获得了缺失其中一个目标基因的疟原虫克隆株，证实该基因对于疟原虫的正常体外培养生长并非必需。针对这些蛋白的抗体可抑制裂殖子对红细胞的侵袭。