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间日疟原虫缅甸分离株中传播阻断疫苗候选抗原Pvs25和Pvs28的遗传多样性与自然选择

Genetic diversity and natural selection of transmission-blocking vaccine candidate antigens Pvs25 and Pvs28 in Plasmodium vivax Myanmar isolates.

作者信息

Lê Hương Giang, Kang Jung-Mi, Jun Hojong, Lee Jinyoung, Moe Mya, Thái Thị Lam, Lin Khin, Myint Moe Kyaw, Yoo Won Gi, Sohn Woon-Mok, Kim Tong-Soo, Na Byoung-Kuk

机构信息

Department of Parasitology and Tropical Medicine, 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.

Department of Tropical Medicine, Inha Research Institute for Medical Sciences, Inha University College of Medicine, Incheon, 22212, Republic of Korea.

出版信息

Acta Trop. 2019 Oct;198:105104. doi: 10.1016/j.actatropica.2019.105104. Epub 2019 Jul 20.

DOI:10.1016/j.actatropica.2019.105104
PMID:31336059
Abstract

Transmission-blocking vaccines (TBVs) target the sexual stages of malarial parasites to interrupt or reduce the transmission cycle have been one of approaches to control malaria. Pvs25 and Pvs28 are the leading candidate antigens of TBVs against vivax malaria. In this study, genetic diversity and natural selection of the two TBV candidate genes in Plasmodium vivax Myanmar isolates were analyzed. The 62 Myanmar P. vivax isolates showed 9 and 19 different haplotypes for Pvs25 and Pvs28, respectively. The nucleotide diversity of Pvs28 was slightly higher than Pvs25, but not significant. Most amino acid substitutions observed in Myanmar Pvs25 and Pvs28 were concentrated at the EGF-2 and EGF-3 like domains. Major amino acid changes found in Myanmar Pvs25 and Pvs28 were similar to those reported in the global population, but novel amino acid substitutions were also identified. Negative selection was predicted in Myanmar Pvs25, whereas Pvs28 was under positive selection. Comparative analysis of global Pvs25 and Pvs28 suggests a substantial geographical difference between the Asian and American/African Pvs25 and Pvs28. The geographical genetic differentiation and the evidence for natural selection in global Pvs25 and Pvs28 suggest that the functional consequences of the observed polymorphism need to be considered for the development of effective TBVs based on the antigens.

摘要

传播阻断疫苗(TBVs)靶向疟原虫的有性阶段以中断或减少传播周期,一直是控制疟疾的方法之一。Pvs25和Pvs28是针对间日疟原虫的传播阻断疫苗的主要候选抗原。在本研究中,分析了缅甸间日疟原虫分离株中这两个传播阻断疫苗候选基因的遗传多样性和自然选择情况。62株缅甸间日疟原虫分离株中,Pvs25和Pvs28分别显示出9种和19种不同的单倍型。Pvs28的核苷酸多样性略高于Pvs25,但差异不显著。在缅甸Pvs25和Pvs28中观察到的大多数氨基酸替换集中在EGF-2和EGF-3样结构域。在缅甸Pvs25和Pvs28中发现的主要氨基酸变化与全球人群中报道的相似,但也鉴定出了新的氨基酸替换。预测缅甸Pvs25受到负选择,而Pvs28受到正选择。对全球Pvs25和Pvs28的比较分析表明,亚洲与美洲/非洲的Pvs25和Pvs28之间存在显著的地理差异。全球Pvs25和Pvs28的地理遗传分化以及自然选择的证据表明,在基于这些抗原开发有效的传播阻断疫苗时,需要考虑观察到的多态性的功能后果。

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