对间日疟原虫 Duffy 结合蛋白的序列分析揭示了埃塞俄比亚分离株中独特单倍型的存在和多样化选择。

Sequence analysis of Plasmodium vivax Duffy binding proteins reveals the presence of unique haplotypes and diversifying selection in Ethiopian isolates.

机构信息

Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia.

Medical Research Council Unit The Gambia At London, School of Hygiene and Tropical Medicin, Banjul, The Gambia.

出版信息

Malar J. 2021 Jul 10;20(1):312. doi: 10.1186/s12936-021-03843-7.

DOI:10.1186/s12936-021-03843-7

PMID:34246262

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8271342/

Abstract

BACKGROUND

Red blood cell invasion by the Plasmodium vivax merozoite requires interaction between the Duffy antigen receptor for chemokines (DARC) and the P. vivax Duffy-binding protein II (PvDBPII). Given that the disruption of this interaction prevents P. vivax blood-stage infection, a PvDBP-based vaccine development has been well recognized. However, the polymorphic nature of PvDBPII prevents a strain transcending immune response and complicates attempts to design a vaccine.

METHODS

Twenty-three P. vivax clinical isolates collected from three areas of Ethiopia were sequenced at the pvdbpII locus. A total of 392 global pvdbpII sequences from seven P. vivax endemic countries were also retrieved from the NCBI archive for comparative analysis of genetic diversity, departure from neutrality, linkage disequilibrium, genetic differentiation, PvDBP polymorphisms, recombination and population structure of the parasite population. To establish a haplotype relationship a network was constructed using the median joining algorithm.

RESULTS

A total of 110 variable sites were found, of which 44 were parsimony informative. For Ethiopian isolates there were 12 variable sites of which 10 were parsimony informative. These parsimony informative variants resulted in 10 nonsynonymous mutations. The overall haplotype diversity for global isolates was 0.9596; however, the haplotype diversity was 0.874 for Ethiopia. Fst values for genetic revealed Ethiopian isolates were closest to Indian isolates as well as to Sri Lankan and Sudanese isolates but further away from Mexican, Papua New Guinean and South Korean isolates. There was a total of 136 haplotypes from the 415 global isolates included for this study. Haplotype prevalence ranged from 36.76% to 0.7%, from this 74.2% were represented by single parasite isolates. None of the Ethiopian isolates grouped with the Sal I reference haplotype. From the total observed nonsynonymous mutations 13 mapped to experimentally verified epitope sequences. Including 10 non-synonymous mutations from Ethiopia. However, all the polymorphic regions in Ethiopian isolates were located away from DARC, responsible for junction formation.

CONCLUSION

The results of this study are concurrent with the multivalent vaccine approach to design an effective treatment. However, the presence of novel haplotypes in Ethiopian isolates that were not shared by other global sequences warrant further investigation.

摘要

背景

恶性疟原虫裂殖子入侵红细胞需要趋化因子的 Duffy 抗原受体（DARC）与恶性疟原虫 Duffy 结合蛋白 II（PvDBPII）之间的相互作用。鉴于这种相互作用的破坏可阻止恶性疟原虫的血期感染，因此已经很好地认识到了基于 PvDBP 的疫苗开发。然而，PvDBPII 的多态性阻止了对菌株的跨越免疫反应，并使设计疫苗的尝试复杂化。

方法

对来自埃塞俄比亚三个地区的 23 株恶性疟原虫临床分离株在 pvdbpII 基因座进行测序。还从 NCBI 档案中检索了来自七个恶性疟原虫流行国家的 392 个全球 pvdbpII 序列，用于比较遗传多样性、偏离中性、连锁不平衡、遗传分化、PvDBP 多态性、重组和寄生虫种群的种群结构。为了建立单倍型关系，使用中位数连接算法构建了一个网络。

结果

共发现 110 个可变位点，其中 44 个为简约信息丰富。对于埃塞俄比亚分离株，有 12 个可变位点，其中 10 个为简约信息丰富。这些简约信息丰富的变体导致 10 个非同义突变。全球分离株的总体单倍型多样性为 0.9596；然而，埃塞俄比亚的单倍型多样性为 0.874。遗传的 Fst 值表明，埃塞俄比亚分离株与印度分离株以及与斯里兰卡和苏丹分离株最接近，但与墨西哥、巴布亚新几内亚和韩国分离株的距离更远。在本研究中包括的 415 个全球分离株中共有 136 个单倍型。单倍型流行率范围为 36.76%至 0.7%，其中 74.2%由单一寄生虫分离株代表。埃塞俄比亚分离株没有一组与 Sal I 参考单倍型聚集。在观察到的非同义突变中，有 13 个映射到经过实验验证的表位序列。其中包括来自埃塞俄比亚的 10 个非同义突变。然而，埃塞俄比亚分离株中所有多态性区域都位于 DARC 之外，负责连接形成。