塞内加尔和冈比亚疟原虫红内期结合蛋白 2b（PfRh2b）的时间变化。
Temporal changes in Plasmodium falciparum reticulocyte binding protein homolog 2b (PfRh2b) in Senegal and The Gambia.
机构信息
Institute for Health Research, Epidemiological Surveillance and Training (IRESSEF), Dakar, Senegal.
Laboratory of Bacteriology and Virology, Hospital Aristide Le Dantec, 7325, Dakar, Senegal.
出版信息
Malar J. 2019 Jul 16;18(1):239. doi: 10.1186/s12936-019-2868-x.
BACKGROUND
The Plasmodium falciparum reticulocyte binding protein homolog 2b (PfRh2b) is an important P. falciparum merozoite ligand that mediates invasion of erythrocytes by interacting with a chymotrypsin-sensitive "receptor Z". A large deletion polymorphism is found in the c-terminal ectodomain of this protein in many countries around the world, resulting in a truncated, but expressed protein. The varying frequencies by region suggest that there could be region specific immune selection at this locus. Therefore, this study was designed to determine temporal changes in the PfRh2b deletion polymorphism in infected individuals from Thiès (Senegal) and Western Gambia (The Gambia). It was also sought to determine the selective pressures acting at this locus and whether prevalence of the deletion in isolates genotyped by a 24-SNP molecular barcode is linked to background genotype or whether there might be independent selection acting at this locus.
METHODS
Infected blood samples were sourced from archives of previous studies conducted between 2007 and 2013 at SLAP clinic in Thiès and from 1984 to 2013 in Western Gambia by MRC Unit at LSHTM, The Gambia. A total of 1380 samples were screened for the dimorphic alleles of the PfRh2b using semi-nested Polymerase Chain Reaction PCR. Samples from Thiès were previously barcoded.
RESULTS
In Thiès, a consistent trend of decreasing prevalence of the PfRh2b deletion over time was observed: from 66.54% in 2007 and to 38.1% in 2013. In contrast, in Western Gambia, the frequency of the deletion fluctuated over time; it increased between 1984 and 2005 from (58.04%) to (69.33%) and decreased to 47.47% in 2007. Between 2007 and 2012, the prevalence of this deletion increased significantly from 47.47 to 83.02% and finally declined significantly to 57.94% in 2013. Association between the presence of this deletion and age was found in Thiès, however, not in Western Gambia. For the majority of isolates, the PfRh2b alleles could be tracked with specific 24-SNP barcoded genotype, indicating a lack of independent selection at this locus.
CONCLUSION
PfRh2b deletion was found in the two countries with varying prevalence during the study period. However, these temporal and spatial variations could be an obstacle to the implementation of this protein as a potential vaccine candidate.
背景
恶性疟原虫（Plasmodium falciparum）裂殖体表面蛋白同源物 2b（PfRh2b）是一种重要的恶性疟原虫配体，通过与一种糜蛋白酶敏感的“受体 Z”相互作用，介导红细胞的入侵。在世界许多国家，该蛋白的 C 端外显子中存在一个大的缺失多态性，导致截短但表达的蛋白。该区域的频率变化表明，该基因座可能存在区域特异性免疫选择。因此，本研究旨在确定塞内加尔蒂埃斯（Thiès）和冈比亚西部（冈比亚）感染个体中 PfRh2b 缺失多态性的时间变化。还试图确定该基因座上的选择压力，以及通过 24-SNP 分子条码分型的分离株中缺失的流行率是否与背景基因型相关，或者是否可能存在独立的选择作用于该基因座。
方法
从塞内加尔蒂埃斯 SLAP 诊所和冈比亚 MRC 单位在 1984 年至 2013 年期间进行的先前研究的档案中采集了感染血样。总共使用半巢式聚合酶链反应 PCR 对 1380 个样本进行了 PfRh2b 二态等位基因的筛选。蒂埃斯的样本之前已经进行了条码标记。
结果
在蒂埃斯，随着时间的推移，PfRh2b 缺失的流行率呈持续下降趋势：从 2007 年的 66.54%下降到 2013 年的 38.1%。相比之下，冈比亚的缺失频率随时间波动；它在 1984 年至 2005 年间从（58.04%）增加到（69.33%），并在 2007 年下降到 47.47%。2007 年至 2012 年间，该缺失的流行率从 47.47%显著增加到 83.02%，最后在 2013 年显著下降到 57.94%。在蒂埃斯，发现该缺失与年龄之间存在关联，但在冈比亚没有。对于大多数分离株，可以用特定的 24-SNP 条码基因型跟踪 PfRh2b 等位基因，表明该基因座不存在独立选择。
结论
在研究期间，在这两个国家发现了 PfRh2b 缺失，其流行率不同。然而，这些时间和空间上的变化可能会对该蛋白作为潜在疫苗候选物的实施构成障碍。
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