Benoît MalleretAbbas El SahiliMatthew Zirui TayGuillaume CarissimoAlice Soh Meoy OngWisna NoveraJianqing LinRossarin SuwanaruskVarakorn KosaisaveeTrang T.T. ChuAmeya SinhaShanshan Wu HowlandYiping FanJakub GruszczykWai Hong ThamYves ColinSebastian Maurer-StrohGeorges SnounouLisa F.P. NgJerry Kok Yen ChanAnn Marie ChackoJulien LescarRajesh ChandramohanadasFrançois NostenBruce RussellLaurent RéniaA-Star, Infectious Disease LabFaculty of Tropical Medicine, Mahidol UniversityUniversité Paris CitéNTU Institute of Structural BiologyA-Star, Singapore Immunology NetworkSingapore University of Technology and DesignSchool of Biological SciencesDuke-NUS Medical SchoolWalter and Eliza Hall Institute of Medical ResearchNUS Yong Loo Lin School of MedicineUniversity of MelbourneA-Star, Bioinformatics InstituteUniversity of OtagoNational University of SingaporeInstitut National de la Transfusion SanguineKK Women's And Children's HospitalMahidol UniversityCEA Fontenay aux RosesNuffield Department of MedicineNanyang Technological University2022-08-042022-08-042021-08-01Nature Microbiology. Vol.6, No.8 (2021), 991-999205852762-s2.0-85111121161https://repository.li.mahidol.ac.th/handle/123456789/76090More 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.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyImmunology and MicrobiologyMedicineArticleSCOPUS10.1038/s41564-021-00939-3