TY - JOUR
T1 - Plasmodium vivax binds host CD98hc (SLC3A2) to enter immature red blood cells
AU - Malleret, Benoît
AU - El Sahili, Abbas
AU - Tay, Matthew Zirui
AU - Carissimo, Guillaume
AU - Ong, Alice Soh Meoy
AU - Novera, Wisna
AU - Lin, Jianqing
AU - Suwanarusk, Rossarin
AU - Kosaisavee, Varakorn
AU - Chu, Trang T.T.
AU - Sinha, Ameya
AU - Howland, Shanshan Wu
AU - Fan, Yiping
AU - Gruszczyk, Jakub
AU - Tham, Wai Hong
AU - Colin, Yves
AU - Maurer-Stroh, Sebastian
AU - Snounou, Georges
AU - Ng, Lisa F.P.
AU - Chan, Jerry Kok Yen
AU - Chacko, Ann Marie
AU - Lescar, Julien
AU - Chandramohanadas, Rajesh
AU - Nosten, François
AU - Russell, Bruce
AU - Rénia, Laurent
N1 - Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2021/8
Y1 - 2021/8
N2 - 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)2–4. 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.
AB - 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)2–4. 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.
UR - http://www.scopus.com/inward/record.url?scp=85111121161&partnerID=8YFLogxK
U2 - 10.1038/s41564-021-00939-3
DO - 10.1038/s41564-021-00939-3
M3 - Article
C2 - 34294905
AN - SCOPUS:85111121161
SN - 2058-5276
VL - 6
SP - 991
EP - 999
JO - Nature Microbiology
JF - Nature Microbiology
IS - 8
ER -