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来自印度尼西亚分离株的间日疟原虫裂殖子表面蛋白 1-42(MSP1-42)片段的遗传多样性:候选 MSP1 疫苗的合理实施。

Genetic diversity of Merozoite surface protein 1-42 (MSP1-42) fragment of Plasmodium vivax from Indonesian isolates: Rationale implementation of candidate MSP1 vaccine.

机构信息

National Institute of Parasitic Diseases, Chinese Centre for Disease Control and Prevention, WHO Collaborating Centre for Tropical Diseases, National Centre for International Research on Tropical Diseases, Key Laboratory of Parasite and Vector Biology of the Chinese Ministry of Health, Shanghai 200025, People's Republic of China; Department of Parasitology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia.

Department of Clinical Pathology and Laboratory Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia.

出版信息

Infect Genet Evol. 2020 Nov;85:104573. doi: 10.1016/j.meegid.2020.104573. Epub 2020 Sep 26.

Abstract

Morbidity and mortality related to malaria in Indonesia are attributed to both Plasmodium falciparum and P. vivax parasites. In addition to vaccines for P. falciparum, vaccines against P. vivax are urgently needed for the prevention of the disease. An extensively studied antigen is the carboxyl-terminus of the 42 kDa region of P. vivax merozoite surface protein-1 (PvMSP1-42). The design of a vaccine based on this antigen requires an understanding of the extent of polymorphism. However, there is no information on the genetic diversity of the antigen in Indonesia. This study aimed to profile the diversity of PvMSP1-42 and its two subdomains (PvMSP1-33 and PvMSP1-19) among Indonesian P. vivax isolates. A total of 52 P. vivax-infected blood samples were collected from patients in two different endemic areas in Indonesia: Banjarmasin (Kalimantan) and Sumba Timur (Nusa Tenggara Timur). The polymorphic characteristics and natural selection of PvMSP1-42 were analyzed using the DnaSP, MEGA, and Structure software. Thirty distinct haplotypes of PvMSP1-42 were identified. They displayed amino acid changes compared to the reference PVP01 sequence. Most of the mutations were concentrated in the 33 kDa fragment. PvMSP1-42 of the Indonesian isolates appeared to be under positive selection. Recombination may also play a role in the resulting genetic diversity of PvMSP1. In conclusion, PvMSP1-42 of Indonesian isolates displayed allelic polymorphisms caused by mutation, recombination, and positive selection. These results will aid the understanding of the P. vivax population in Indonesia and to develop a PvMSP1 based vaccine against P. vivax.

摘要

印度尼西亚疟疾的发病率和死亡率与恶性疟原虫和间日疟原虫寄生虫有关。除了恶性疟原虫疫苗外,还迫切需要针对间日疟原虫的疫苗来预防这种疾病。一种经过广泛研究的抗原是间日疟原虫裂殖子表面蛋白-1(PvMSP1-42)羧基末端。基于该抗原设计疫苗需要了解其多态性的程度。然而,目前尚无关于印度尼西亚抗原遗传多样性的信息。本研究旨在分析印度尼西亚间日疟原虫分离株中 PvMSP1-42 及其两个亚结构域(PvMSP1-33 和 PvMSP1-19)的多样性。共采集了来自印度尼西亚两个不同流行地区(Banjarmasin [Kalimantan]和 Sumba Timur [Nusa Tenggara Timur])间日疟原虫感染者的 52 份血液样本。使用 DnaSP、MEGA 和 Structure 软件分析了 PvMSP1-42 的多态性特征和自然选择。鉴定出 30 种不同的 PvMSP1-42 单倍型。它们与参考 PVP01 序列相比显示出氨基酸变化。大多数突变集中在 33 kDa 片段。印度尼西亚分离株的 PvMSP1-42 似乎受到正选择的影响。重组也可能在 PvMSP1 遗传多样性的结果中发挥作用。总之,印度尼西亚分离株的 PvMSP1-42 显示出由突变、重组和正选择引起的等位基因多态性。这些结果将有助于了解印度尼西亚的间日疟原虫种群,并开发针对间日疟原虫的 PvMSP1 疫苗。

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