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巴西亚马逊五个不同地区田间分离株中富含半胱氨酸的保护性抗原(PvCyRPA)的遗传多样性。

Genetic Diversity of Cysteine-Rich Protective Antigen (PvCyRPA) in Field Isolates from Five Different Areas of the Brazilian Amazon.

机构信息

Laboratory of Immunoparasitology, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 21040-900, Brazil.

Laboratory of Basic and Applied Immunology, Arthur Sá Earp Neto University Center, Petrópolis 25680-120, Brazil.

出版信息

Genes (Basel). 2021 Oct 21;12(11):1657. doi: 10.3390/genes12111657.

Abstract

The Cysteine-Rich Protective Antigen (PvCyRPA) has an important role in erythrocyte invasion and has been considered a target for malaria vaccine development. Nonetheless, its genetic diversity remains uncharted in Brazilian malaria-endemic areas. Therefore, we investigated the genetic polymorphism in 98 field isolates from the Brazilian Amazon and its impact on the antigenicity of predicted B-cell epitopes. Genetic diversity parameters, population genetic analysis, neutrality test and the median-joining network were analyzed, and the potential amino acid polymorphism participation in B-cell epitopes was investigated. One synonymous and 26 non-synonymous substitutions defined fifty haplotypes. The nucleotide diversity and Tajima's D values varied across the coding gene. The exon-1 sequence had greater diversity than those of exon-2. Concerning the prediction analysis, seven sequences were predicted as linear B cell epitopes, the majority contained in conformational epitopes. Moreover, important amino acid polymorphism was detected in regions predicted to contain residues participating in B-cell epitopes. Our data suggest that the gene presents a moderate polymorphism in the studied isolates and such polymorphisms alter amino acid sequences contained in potential B cell epitopes, an important observation considering the antigen potentiality as a vaccine candidate to cover distinct endemic areas worldwide.

摘要

富含半胱氨酸的保护性抗原(PvCyRPA)在红细胞入侵中具有重要作用,已被认为是疟疾疫苗开发的一个目标。尽管如此,其遗传多样性在巴西疟疾流行地区仍未被发现。因此,我们研究了来自巴西亚马逊地区的 98 个现场分离株中的遗传多态性及其对预测 B 细胞表位抗原性的影响。分析了遗传多样性参数、群体遗传分析、中性检验和中位数连接网络,并研究了潜在的氨基酸多态性参与 B 细胞表位的情况。一个同义突变和 26 个非同义突变定义了 50 个单倍型。编码基因的核苷酸多样性和 Tajima's D 值各不相同。外显子 1 的序列比外显子 2 的序列多样性更大。关于预测分析,有七个序列被预测为线性 B 细胞表位,其中大多数包含在构象表位中。此外,在预测含有参与 B 细胞表位的残基的区域中检测到重要的氨基酸多态性。我们的数据表明,在所研究的分离株中,该基因存在中度的多态性,这种多态性改变了潜在 B 细胞表位中包含的氨基酸序列,这一观察结果对于作为疫苗候选物的抗原潜力考虑到在全球不同的流行地区具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6ac/8623135/7a3c9d595107/genes-12-01657-g001.jpg

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