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

Benoît Malleret (1) , Abbas El Sahili (2) , Matthew Zirui Tay , Guillaume Carissimo (3) , Alice Soh Meoy Ong , Wisna Novera , Jianqing Lin , Rossarin Suwanarusk (4) , Varakorn Kosaisavee , Trang Chu , Ameya Sinha , Shanshan Wu Howland , Yiping Fan , Jakub Gruszczyk , Wai-Hong Tham , Yves Colin (5) , Sebastian Maurer-Stroh , Georges Snounou (6) , Lisa Ng , Jerry Kok Yen Chan , Ann-Marie Chacko , Julien Lescar , Rajesh Chandramohanadas , François Nosten , Bruce Russell , Laurent Rénia

1 IMETI - Institut des Maladies Emergentes et des Thérapies Innovantes
2 I2BC - Institut de Biologie Intégrative de la Cellule
3 A*STAR - Agency for science, technology and research [Singapore]
4 Global Health Division
5 BIGR (UMR_S_1134 / U1134) - Biologie Intégrée du Globule Rouge
6 IMVA-HB - Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes

Plasmodium vivax malaria, mainly in Asia1. 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 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.

Mots clés: Malaria; Invasion; Reticulocyte; Ligand; Receptor; Plasmodium vivax

Domaines: Parasitologie; Interactions cellulaires [q-bio.CB]

Benoît Malleret, Abbas El Sahili, Matthew Zirui Tay, Guillaume Carissimo, Alice Soh Meoy Ong, et al.. Plasmodium vivax binds host CD98hc (SLC3A2) to enter immature red blood cells. Nature Microbiology, 2021, 6 (8), pp.991-999. ⟨10.1038/s41564-021-00939-3⟩. ⟨hal-03448619⟩