Plasmodium vivax binds host CD98hc (SLC3A2) to enter immature red blood cells

Malleret, B; El Sahili, A; Tay, MZ; Carissimo, G; Ong, ASM; Novera, W; Lin, J; Suwanarusk, R; Kosaisavee, V; Chu, TTT; Sinha, A; Howland, SW; Fan, Y; Gruszczyk, J; Tham, WH; Colin, Y; Maurer-Stroh, S; Snounou, G; Ng, LFP; Chan, JKY; Chacko, AM; Lescar, J; Chandramohanadas, R; Nosten, F; Russell, B; R&#233;nia, L

Author(s): Malleret, B; El Sahili, A; Tay, MZ; Carissimo, G; Ong, ASM; Novera, W; Lin, J; Suwanarusk, R; Kosaisavee, V; Chu, TTT; Sinha, A; Howland, SW; Fan, Y; Gruszczyk, J; Tham, WH; Colin, Y; Maurer-Stroh, S; Snounou, G; Ng, LFP; Chan, JKY; Chacko, AM; Lescar, J; Chandramohanadas, R; Nosten, F; Russell, B; Rénia, L;
Details: Publication Year 2021-08,Volume 6,Issue #8,Page 991-999
Journal Title: Nature Microbiology
Abstract: More than one-third of the world's population is exposed to Plasmodium vivax malaria, mainly in Asia(1). P. vivax preferentially invades reticulocytes (immature red blood cells)(2-4). Previous work has identified 11 parasite proteins involved in reticulocyte invasion, including erythrocyte binding protein 2 (ref. (5)) and the reticulocyte-binding proteins (PvRBPs)(6-10). PvRBP2b binds to the transferrin receptor CD71 (ref. (11)), which is selectively expressed on immature reticulocytes(12). 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.
Publisher: NPG
Keywords: Antigens, CD; Antigens, Protozoan/genetics/metabolism; Erythrocytes/metabolism/*parasitology; Fusion Regulatory Protein 1, Heavy Chain/genetics/*metabolism; Host-Parasite Interactions; Humans; Malaria, Vivax/blood/genetics/*metabolism; Plasmodium vivax/genetics/*metabolism; Protein Binding; Protozoan Proteins/genetics/metabolism; Receptors, Cell Surface/genetics/metabolism; Receptors, Transferrin; Reticulocytes/metabolism/parasitology
Research Division(s): Infectious Diseases And Immune Defence
PubMed ID: 34294905
Publisher's Version: https://doi.org/10.1038/s41564-021-00939-3
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2021-10-12 07:30:11

Last Modified: 2021-10-19 11:14:12