赤道几内亚比奥科岛疟原虫环子孢子蛋白的遗传多态性及其全球比较分析。

Genetic polymorphism of Plasmodium falciparum circumsporozoite protein on Bioko Island, Equatorial Guinea and global comparative analysis.

机构信息

School of Food Engineering and Biotechnology, Hanshan Normal University, Chaozhou, People's Republic of China.

Department of Medical Genetics, Shantou University Medical College, Shantou, Guangdong Province, People's Republic of China.

出版信息

Malar J. 2020 Jul 13;19(1):245. doi: 10.1186/s12936-020-03315-4.

BACKGROUND

Plasmodium falciparum circumsporozoite protein (PfCSP) is a potential malaria vaccine candidate, but various polymorphisms of the pfcsp gene among global P. falciparum population become the major barrier to the effectiveness of vaccines. This study aimed to investigate the genetic polymorphisms and natural selection of pfcsp in Bioko and the comparison among global P. falciparum population.

METHODS

From January 2011 to December 2018, 148 blood samples were collected from P. falciparum infected Bioko patients and 96 monoclonal sequences of them were successfully acquired and analysed with 2200 global pfcsp sequences mined from MalariaGEN Pf3k Database and NCBI.

RESULTS

In Bioko, the N-terminus of pfcsp showed limited genetic variations and the numbers of repetitive sequences (NANP/NVDP) were mainly found as 40 (35%) and 41 (34%) in central region. Most polymorphic characters were found in Th2R/Th3R region, where natural selection (p > 0.05) and recombination occurred. The overall pattern of Bioko pfcsp gene had no obvious deviation from African mainland pfcsp (Fst = 0.00878, p < 0.05). The comparative analysis of Bioko and global pfcsp displayed the various mutation patterns and obvious geographic differentiation among populations from four continents (p < 0.05). The global pfcsp C-terminal sequences were clustered into 138 different haplotypes (H_1 to H_138). Only 3.35% of sequences matched 3D7 strain haplotype (H_1).

CONCLUSIONS

The genetic polymorphism phenomena of pfcsp were found universal in Bioko and global isolates and the majority mutations located at T cell epitopes. Global genetic polymorphism and geographical characteristics were recommended to be considered for future improvement of malaria vaccine design.

背景

恶性疟原虫环子孢子蛋白（PfCSP）是一种有潜力的疟疾疫苗候选物，但全球恶性疟原虫群体中 PfCSP 基因的各种多态性成为疫苗有效性的主要障碍。本研究旨在调查比奥科岛 PfCSP 的遗传多态性和自然选择，并比较全球恶性疟原虫群体。

方法

2011 年 1 月至 2018 年 12 月，采集了来自恶性疟原虫感染比奥科岛患者的 148 份血液样本，并成功获得了其中的 96 个单克隆序列，并与从 MalariaGEN Pf3k 数据库和 NCBI 挖掘的 2200 个全球 PfCSP 序列进行分析。

结果

在比奥科岛，PfCSP 的 N 端显示出有限的遗传变异，中央区域中主要发现重复序列（NANP/NVDP）为 40（35%）和 41（34%）。Th2R/Th3R 区域存在大多数多态性特征，发生了自然选择（p>0.05）和重组。比奥科岛 PfCSP 基因的整体模式与非洲大陆 PfCSP 没有明显偏差（Fst=0.00878，p<0.05）。比奥科岛与全球 PfCSP 的比较分析显示，来自四大洲的人群存在各种突变模式和明显的地理分化（p<0.05）。全球 PfCSP 的 C 端序列聚类为 138 个不同的单倍型（H_1 到 H_138）。只有 3.35%的序列与 3D7 株单倍型（H_1）匹配。