Nedaei Fatemeh, Noormohammadi Zahra, Naddaf Saied Reza, Mohammadi Somayeh, Esmaeili Rastaghi Ahmad Reza
Department of Parasitology, Pasteur Institute of Iran, Tehran, Iran.
Department of Biology , College of Basic Science Islamic Azad University, Science and Research Branch, Tehran, Iran.
Int J Mol Cell Med. 2017 Fall;6(4):222-234. doi: 10.22088/BUMS.6.4.222. Epub 2017 Nov 16.
apical membrane antigen-1(PvAMA-1) is a surface protein with polymorphic sites. This study was aimed to analyze the polymorphic amino acid residues at PvAMA-1 in different infected age groups. 92 blood samples were collected from the south and southeast of Iran. The DNA coding for the domain I (DI), DII, and partial DIII of this antigen was amplified by Nested-PCR, and sequenced. Nucleotide mutations were found in 49 sites and based on the amino acid sequence, 30 variable sites were detected. Age distribution of malaria cases showed that the majority of the patients were between 10 to 30 years old. The scattering plot haplotypes by age showed an increasing incidence rate with age during childhood, whereas, incidence was the lowest in patients under five years old. Comparison of the polymorphic sites of PvAMA-1 in Iranian isolates with those found in other geographic regions of the world indicated nine common variable positions. In addition, a significant dependence was found between some particular substitutions and age categories. Dependence between particular substitutions and age groups suggests that certain residues in AMA-1 are responsible for clinical attacks in different ages, likely as a result of host immune pressure. The crystal structure of the PvAMA-1 showed that the amino acid substitutions that changed the protein charge were exclusively located in loops and turns where, the interactions with antibodies could occur. These data provide the necessary information for an AMA-1 based malaria vaccine design to be effective across all ages.
顶端膜抗原-1（PvAMA-1）是一种具有多态性位点的表面蛋白。本研究旨在分析不同感染年龄组中PvAMA-1的多态性氨基酸残基。从伊朗南部和东南部采集了92份血样。通过巢式PCR扩增该抗原的结构域I（DI）、DII和部分DIII的编码DNA，并进行测序。在49个位点发现了核苷酸突变，基于氨基酸序列，检测到30个可变位点。疟疾病例的年龄分布表明，大多数患者年龄在10至30岁之间。按年龄绘制的散点图单倍型显示，儿童期发病率随年龄增加，而5岁以下患者的发病率最低。将伊朗分离株中PvAMA-1的多态性位点与世界其他地理区域发现的多态性位点进行比较，发现有9个共同的可变位置。此外，还发现一些特定替换与年龄类别之间存在显著相关性。特定替换与年龄组之间的相关性表明，AMA-1中的某些残基在不同年龄的临床发作中起作用，这可能是宿主免疫压力的结果。PvAMA-1的晶体结构表明，改变蛋白质电荷的氨基酸替换仅位于环和转角处，在这些位置可能发生与抗体的相互作用。这些数据为基于AMA-1的疟疾疫苗设计提供了必要信息，使其在所有年龄段都有效。
