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缅甸疟原虫裂殖子表面蛋白-1 和裂殖子表面蛋白-2 遗传多样性的变化模式。

Changing pattern of the genetic diversities of Plasmodium falciparum merozoite surface protein-1 and merozoite surface protein-2 in Myanmar isolates.

机构信息

Department of Parasitology and Tropical Medicine, and Institute of Health Sciences, Gyeongsang National University College of Medicine, Jinju, 52727, Republic of Korea.

BK21Plus Team for Anti-aging Biotechnology and Industry, Department of Convergence Medical Science, Gyeongsang National University, Jinju, 52727, Republic of Korea.

出版信息

Malar J. 2019 Jul 16;18(1):241. doi: 10.1186/s12936-019-2879-7.

Abstract

BACKGROUND

Plasmodium falciparum merozoite surface protein-1 (PfMSP-1) and -2 (PfMSP-2) are major blood-stage vaccine candidate antigens. Understanding the genetic diversity of the genes, pfmsp-1 and pfmsp-2, is important for recognizing the genetic structure of P. falciparum, and the development of an effective vaccine based on the antigens. In this study, the genetic diversities of pfmsp-1 and pfmsp-2 in the Myanmar P. falciparum were analysed.

METHODS

The pfmsp-1 block 2 and pfmsp-2 block 3 regions were amplified by polymerase chain reaction from blood samples collected from Myanmar patients who were infected with P. falciparum in 2013-2015. The amplified gene fragments were cloned into a T&A vector, and sequenced. Sequence analysis of Myanmar pfmsp-1 block 2 and pfmsp-2 block 3 was performed to identify the genetic diversity of the regions. The temporal genetic changes of both pfmsp-1 and pfmsp-2 in the Myanmar P. falciparum population, as well as the polymorphic diversity in the publicly available global pfmsp-1 and pfmsp-2, were also comparatively analysed.

RESULTS

High levels of genetic diversity of pfmsp-1 and pfmsp-2 were observed in the Myanmar P. falciparum isolates. Twenty-eight different alleles of pfmsp-1 (8 for K1 type, 14 for MAD20 type, and 6 for RO33 type) and 59 distinct alleles of pfmsp-2 (18 for FC27, and 41 for 3D7 type) were identified in the Myanmar P. falciparum population in amino acid level. Comparative analyses of the genetic diversity of the Myanmar pfmsp-1 and pfmsp-2 alleles in the recent (2013-2015) and past (2004-2006) Myanmar P. falciparum populations indicated the dynamic genetic expansion of the pfmsp-1 and pfmsp-2 in recent years, suggesting that a high level of genetic differentiation and recombination of the two genes may be maintained. Population genetic structure analysis of the global pfmsp-1 and pfmsp-2 also suggested that a high level of genetic diversity of the two genes was found in the global P. falciparum population.

CONCLUSION

Despite the recent remarkable decline of malaria cases, the Myanmar P. falciparum population still remains of sufficient size to allow the generation and maintenance of genetic diversity. The high level of genetic diversity of pfmsp-1 and pfmsp-2 in the global P. falciparum population emphasizes the necessity for continuous monitoring of the genetic diversity of the genes for better understanding of the genetic make-up and evolutionary aspect of the genes in the global P. falciparum population.

摘要

背景

恶性疟原虫裂殖子表面蛋白-1(PfMSP-1)和-2(PfMSP-2)是主要的血阶段候选疫苗抗原。了解基因 pfmsp-1 和 pfmsp-2 的遗传多样性对于识别恶性疟原虫的遗传结构以及基于抗原开发有效的疫苗非常重要。本研究分析了缅甸恶性疟原虫 pfmsp-1 和 pfmsp-2 的遗传多样性。

方法

从 2013-2015 年在缅甸感染恶性疟原虫的患者的血液样本中,通过聚合酶链反应扩增 pfmsp-1 块 2 和 pfmsp-2 块 3 区。将扩增的基因片段克隆到 T&A 载体中,并进行测序。对缅甸 pfmsp-1 块 2 和 pfmsp-2 块 3 进行序列分析,以确定这些区域的遗传多样性。还比较分析了缅甸恶性疟原虫种群中 pfmsp-1 和 pfmsp-2 的时间遗传变化以及全球公开的 pfmsp-1 和 pfmsp-2 的多态性多样性。

结果

在缅甸恶性疟原虫分离株中观察到 pfmsp-1 和 pfmsp-2 的遗传多样性水平较高。在缅甸恶性疟原虫种群中,在氨基酸水平上鉴定出 28 种不同的 pfmsp-1 等位基因(8 种 K1 型,14 种 MAD20 型,6 种 RO33 型)和 59 种不同的 pfmsp-2 等位基因(18 种 FC27 型,41 种 3D7 型)。对最近(2013-2015 年)和过去(2004-2006 年)缅甸恶性疟原虫种群中缅甸 pfmsp-1 和 pfmsp-2 等位基因遗传多样性的比较分析表明,近年来 pfmsp-1 和 pfmsp-2 的遗传扩张明显,表明这两个基因可能保持着较高的遗传分化和重组水平。对全球 pfmsp-1 和 pfmsp-2 的种群遗传结构分析也表明,全球恶性疟原虫种群中这两个基因的遗传多样性水平较高。

结论

尽管疟疾病例最近显著下降,但缅甸恶性疟原虫种群仍然足够大,能够产生和维持遗传多样性。全球恶性疟原虫种群中 pfmsp-1 和 pfmsp-2 的高水平遗传多样性强调了需要持续监测这些基因的遗传多样性,以更好地了解全球恶性疟原虫种群中这些基因的遗传结构和进化方面。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa00/6636015/8645fcac050e/12936_2019_2879_Fig1_HTML.jpg

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