Erythrocyte invasion phenotypes of Plasmodium falciparum in the Gambia
Erythrocyte invasion phenotypes of Plasmodium falciparum in the Gambia
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DOI：
10.1128/iai.71.4.1856-1863.2003
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发表时间：
2003-04-01
影响因子：
3.1
通讯作者：
Conway, DJ
中科院分区：
文献类型：
--
作者：
Baum, J;Pinder, M;Conway, DJ
恶性疟原虫的体外实验已经确定，许多不同的受体-配体相互作用参与红细胞的侵袭。大多数培养适应的寄生虫分离株使用主要依赖于寄生虫血液期裂殖子的红细胞唾液酸糖蛋白血型糖蛋白A（GYPA）和红细胞结合抗原175（EBA-175）的侵入机制。然而，少数适应文化的寄生虫和大多数印度田间分离株显然可以通过其他方式入侵。在这里，红细胞侵入表型的恶性疟原虫在非洲的现场分离进行了研究。对于38冈比亚分离株，神经氨酸酶处理和胰蛋白酶处理的红细胞的侵袭被抑制，平均超过60%和85%，分别表示高水平的依赖唾液酸和胰蛋白酶敏感的蛋白质的红细胞表面。这些结果支持了非洲恶性疟原虫利用GYPA作为入侵主要受体的假设。然而，分离物之间的相当大的差异证实了许多寄生虫也使用替代受体的想法。EBA-175的GYPA结合区（区域II）的三个氨基酸多态性与侵袭表型没有显著相关。分离株之间的选择性指数存在差异（即，宿主红细胞聚集或多重侵袭的统计学趋势），但这种变异与酶决定的侵袭表型或EBA-175等位基因无关。总的来说，非洲的这些入侵表型支持抑制EBA-175与GYPA结合的疫苗策略，但表明如果单独使用该策略，将选择具有替代表型的寄生虫。
In vitro experimentation with Plasmodium falciparum has determined that a number of different receptor-ligand interactions are involved in the invasion of erythrocytes. Most culture-adapted parasite isolates use a mechanism of invasion that depends primarily on the erythrocyte sialoglycoprotein glycophorin A (GYPA) and erythrocyte-binding antigen 175 (EBA-175) of the parasite blood-stage merozoite. However, a minority of culture-adapted parasites and a majority of Indian field isolates can apparently invade by other means. Here, erythrocyte invasion phenotypes of P. falciparum field isolates in Africa were studied. For 38 Gambian isolates, invasion of neuraminidase-treated and trypsin-treated erythrocytes was inhibited, on average, by more than 60 and 85%, respectively, indicating a high level of dependence on sialic acid and trypsin-sensitive proteins on the erythrocyte surface. These results support the hypothesis that African P. falciparum parasites use GYPA as a primary receptor for invasion. However, the considerable variation among isolates confirms the idea that alternative receptors are also used by many parasites. Three amino acid polymorphisms in the GYPA-binding region of EBA-175 (region II) were not significantly associated with invasion phenotype. There was variation among isolates in the selectivity index (i.e., a statistical tendency toward aggregation or multiple invasions of host erythrocytes), but this variation did not correlate with enzyme-determined invasion phenotype or with eba-175 alleles. Overall, these invasion phenotypes in Africa support a vaccine strategy of inhibiting EBA-175 binding to GYPA but suggest that parasites with alternative phenotypes would be selected for if this strategy were used alone.