The erythrocyte silent Duffy blood group phenotype in Africans is thought to confer resistance to Plasmodium vivax blood-stage infection. However, recent studies report P. vivax infections across Africa in Fy-negative individuals. This suggests that the globin transcription factor 1 (GATA-1) SNP underlying Fy negativity does not entirely abolish Fy expression or that P. vivax has developed a Fy-independent red blood cell (RBC) invasion pathway. We show that RBCs and erythroid progenitors from in vitro differentiated CD34 cells and from bone marrow aspirates from Fy-negative samples express a functional Fy on their surface. This suggests that the GATA-1 SNP does not entirely abolish Fy expression. Given these results, we developed an in vitro culture system for P. vivax and show P. vivax can invade erythrocytes from Duffy-negative individuals. This study provides evidence that Fy is expressed in Fy-negative individuals and explains their susceptibility to P. vivax with major implications and challenges for P. vivax malaria eradication.

非洲人的红细胞沉默达菲血型表型被认为具有对间日疟原虫血期感染的抵抗力。然而，最近的研究报告称，整个非洲的 Fy 阴性个体均感染间日疟原虫。这表明导致 Fy 阴性的球蛋白转录因子 1 (GATA-1) SNP 并未完全消除 Fy 表达，或者间日疟原虫已经形成了一条不依赖于 Fy 的红细胞 (RBC) 入侵途径。我们发现，来自体外分化的 CD34 细胞和 Fy 阴性样本的骨髓抽吸物的红细胞和红系祖细胞在其表面表达功能性 Fy。这表明 GATA-1 SNP 并未完全消除 Fy 表达。鉴于这些结果，我们开发了一种间日疟原虫体外培养系统，并表明间日疟原虫可以侵入达菲阴性个体的红细胞。这项研究提供了 Fy 在 Fy 阴性个体中表达的证据，并解释了他们对间日疟原虫的易感性，这对根除间日疟原虫疟疾具有重大影响和挑战。