More than one-third of the world’s population is exposed to Plasmodium vivax malaria, mainly in Asia¹. P. vivax preferentially invades reticulocytes (immature red blood cells)^2,3,4. Previous work has identified 11 parasite proteins involved in reticulocyte invasion, including erythrocyte binding protein 2 (ref. ⁵) and the reticulocyte-binding proteins (PvRBPs)^6,7,8,9,10. PvRBP2b binds to the transferrin receptor CD71 (ref. ¹¹), which is selectively expressed on immature reticulocytes¹². Here, we identified CD98 heavy chain (CD98), a heteromeric amino acid transporter from the SLC3 family (also known as SLCA2), as a reticulocyte-specific receptor for the PvRBP2a parasite ligand using mass spectrometry, flow cytometry, biochemical and parasite invasion assays. We characterized the expression level of CD98 at the surface of immature reticulocytes (CD71⁺) and identified an interaction between CD98 and PvRBP2a expressed at the merozoite surface. Our results identify CD98 as an additional host membrane protein, besides CD71, that is directly associated with P. vivax reticulocyte tropism. These findings highlight the potential of using PvRBP2a as a vaccine target against P. vivax malaria.

世界上超过三分之一的人口暴露于间日疟原虫疟疾，主要在亚洲¹。间日疟原虫优先侵入网织红细胞（未成熟​​的红细胞）^2,3,4。以前的工作已经确定了 11 种参与网织红细胞侵袭的寄生虫蛋白，包括红细胞结合蛋白 2（参考文献⁵）和网织红细胞结合蛋白 (PvRBPs) ^6,7,8,9,10。PvRBP2b 与转铁蛋白受体 CD71（参考文献¹¹）结合，该受体在未成熟网织红细胞上选择性表达¹². 在这里，我们使用质谱、流式细胞术、生化和寄生虫入侵检测鉴定了 CD98 重链 (CD98)，一种来自 SLC3 家族（也称为 SLCA2）的异聚氨基酸转运蛋白，作为 PvRBP2a 寄生虫配体的网织红细胞特异性受体. ^{我们表征了未成熟网织红细胞 (CD71 +} )表面 CD98 的表达水平，并确定了 CD98 和裂殖子表面表达的 PvRBP2a 之间的相互作用。我们的结果将 CD98 确定为除了 CD71 之外的一种额外的宿主膜蛋白，它与间日疟原虫网织红细胞嗜性直接相关。这些发现突出了使用 PvRBP2a 作为针对间日疟原虫的疫苗靶标的潜力。