VAR2CSA Signatures of High Plasmodium falciparum Parasitemia in the Placenta

Plasmodium falciparum infected erythrocytes (IE) accumulate in the placenta through the interaction between Duffy-binding like (DBL) domains of parasite-encoded ligand VAR2CSA and chondroitin sulphate-A (CSA) receptor. Polymorphisms in these domains, including DBL2X and DBL3X, may affect their antigenicity or CSA-binding affinity, eventually increasing parasitemia and its adverse effects on pregnancy outcomes. A total of 373 DBL2X and 328 DBL3X sequences were obtained from transcripts of 20 placental isolates infecting Mozambican women, resulting in 176 DBL2X and 191 DBL3X unique sequences at the protein level. Sequence alignments were divided in segments containing combinations of correlated polymorphisms and the association of segment sequences with placental parasite density was tested using Bonferroni corrected regression models, taking into consideration the weight of each sequence in the infection. Three DBL2X and three DBL3X segments contained signatures of high parasite density (P

恶性疟原虫（Plasmodium falciparum）感染的红细胞（IE）可通过寄生虫编码配体VAR2CSA的达菲结合样（DBL）结构域与硫酸软骨素A（CSA）受体的相互作用，在胎盘中聚集定植。这些结构域（包括DBL2X和DBL3X）中的多态性可能影响其抗原性或CSA结合亲和力，最终升高虫血症水平并加重对妊娠结局的不良影响。本研究从感染莫桑比克女性的20株胎盘分离株的转录本中，共获取373条DBL2X序列与328条DBL3X序列；经蛋白质水平分析，最终得到176条独特DBL2X序列与191条独特DBL3X序列。研究人员将序列比对结果划分为包含相关多态性组合的片段，并采用邦费罗尼（Bonferroni）校正回归模型，结合每条序列在感染中的权重，检验片段序列与胎盘寄生虫密度之间的关联。共3个DBL2X片段与3个DBL3X片段呈现出高胎盘寄生虫密度的特征（P