The erythrocyte binding motif of Plasmodium vivax Duffy binding protein is highly polymorphic and functionally conserved in isolates from Papua New Guinea
The erythrocyte binding motif of Plasmodium vivax Duffy binding protein is highly polymorphic and functionally conserved in isolates from Papua New Guinea
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DOI：
10.1016/s0166-6851(00)00315-7
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发表时间：
2000-12-01
影响因子：
1.5
通讯作者：
King, CL
中科院分区：
文献类型：
--
作者：
Jia, XL;Adams, JH;King, CL
间日疟原虫的达菲结合蛋白（DBP）是一种关键的粘附配体，参与裂殖子侵入人达菲阳性网织红细胞。结合结构域已被证明位于保守的 N 端富含半胱氨酸的区域（区域 II）内，该区域包含 330 个氨基酸，并且关键的结合残基最近已被定位到该区域内的 170 个氨基酸序列。先前对少数分离株的研究表明 II 区 (DBPII) 存在显着程度的多态性。为了进一步检查 DBPII 的变异程度以及这些变异是否产生功能变化，通过巢式 PCR 从巴布亚新几内亚的 24 个分离株中扩增 DBPII，并对扩增子进行克隆和测序。鉴定出 1 个同义突变和 18 个非同义突变。总共，93% 的累积多态性位于 170 个氨基酸区域内。 Cos7细胞表面两个不同等位基因的区域II的靶向表面表达不影响它们与达菲阳性红细胞的结合。这些结果表明关键结合基序的多态性不会改变其功能。如果 DBPII 变异的出现是为了避免针对 DBP 的保护性免疫机制，那么采用寄生虫结合配体的疫苗开发可能需要采取策略来最大限度地减少这种多态性的影响。 (C) 2000 Elsevier Science B.V. 保留所有权利。
The Duffy binding protein (DBP) of Plasmodium vivax is a critical adhesion ligand that participates in merozoite invasion of human Duffy positive reticulocytes. Binding domains have been shown to lie within a conserved N-terminal cyteine-rich region, region II, that contains 330-aa and the critical binding residues have been recently mapped to 170-aa stretch within this region. Previous studies on few isolates indicated a significant degree of polymorphism in region II (DBPII). To examine further the degree of variability of DBPII, and whether these variants produce functional changes, DBPII was amplified by nested PCR from 24 isolates from Papua New Guinea, and the amplicons were cloned and sequenced. One synonymous and 18 non-synonymous mutations were identified. Altogether, 93% of the cumulative polymorphisms lie within the 170-aa region. Targeted surface expression of region II of two different alleles on the surface of Cos7 cells did not affect their binding to Duffy positive erythrocytes. These results indicate that polymorphisms in the critical binding motifs do not alter its function. If DBPII variation arose to avert mechanisms of protective immunity targeting the DBP, vaccine development employing the parasite binding ligand may require strategies to minimize the effect of this polymorphism. (C) 2000 Elsevier Science B.V. All rights reserved.