寄生虫间日疟原虫优先侵入人网织红细胞。其裂殖子表面蛋白1旁系(PvMSP1P),特别是19kDaC末端区域(PvMSP1P-19),已显示与网织红细胞结合,并且可以通过PvMSP1P-19免疫获得的抗血清抑制这种结合。间日疟原虫入侵过程中PvMSP1P-19与网织红细胞相互作用的分子机制,然而,尚不清楚。在这项研究中,我们分析了MSP1P-19与不同浓度网织红细胞结合的能力,并证实了其网织红细胞的偏好。LC-MS分析用于鉴定两种潜在的网织红细胞受体,band3和CD71,与MSP1P-19相互作用。发现PvMSP1P-19及其姐妹分类单元食蟹性疟原虫MSP1P-19(PcMSP1P-19)均与band3的胞外环(环5)结合,其中MSP1P-19与band3的相互作用对胰凝乳蛋白酶敏感。针对band3-P5,CD71和MSP1P-19的抗体降低了PvMSP1P-19和PcMSP1P-19与网织红细胞的结合活性,而MSP1P-19蛋白在体外以浓度依赖的方式抑制恶性疟原虫的侵袭。总而言之,网织红细胞受体的鉴定和表征对于了解MSP1P-19与网织红细胞的结合非常重要。
The parasite Plasmodium vivax preferentially invades human
reticulocytes. Its merozoite surface protein 1 paralog (PvMSP1P), particularly the 19-kDa C-terminal region (PvMSP1P-19), has been shown to bind to
reticulocytes, and this binding can be inhibited by antisera obtained by PvMSP1P-19 immunization. The molecular mechanism of interactions between PvMSP1P-19 and
reticulocytes during P. vivax invasion, however, remains unclear. In this study, we analyzed the ability of MSP1P-19 to bind to different concentrations of
reticulocytes and confirmed its reticulocyte preference. LC-MS analysis was used to identify two potential reticulocyte receptors, band3 and CD71, that interact with MSP1P-19. Both PvMSP1P-19 and its sister taxon Plasmodium cynomolgi MSP1P-19 were found to bind to the extracellular loop (loop 5) of band3, where the interaction of MSP1P-19 with band3 was chymotrypsin sensitive. Antibodies against band3-P5, CD71, and MSP1P-19 reduced the binding activity of PvMSP1P-19 and Plasmodium cynomolgi MSP1P-19 to
reticulocytes, while MSP1P-19 proteins inhibited Plasmodium falciparum invasion in vitro in a concentration-dependent manner. To sum up, identification and characterization of the reticulocyte receptor is important for understanding the binding of reticulocytes by MSP1P-19.