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

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

Journal: Nature microbiology 2021;6(8):991-999

PMID: 34294905

Full Text on Nature Publishing Group View on PubMed

Abstract

More than one-third of the world's population is exposed to Plasmodium vivax malaria, mainly in Asia. P. vivax preferentially invades reticulocytes (immature red blood cells). Previous work has identified 11 parasite proteins involved in reticulocyte invasion, including erythrocyte binding protein 2 (ref. ) and the reticulocyte-binding proteins (PvRBPs). PvRBP2b binds to the transferrin receptor CD71 (ref. ), which is selectively expressed on immature reticulocytes. 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.

Address: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore. [email protected].; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. [email protected].; Immunology Translational Research Programme, Yong Loo Lin School of Medicine, Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore, Singapore. [email protected].; School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.; NTU Institute for Structural Biology, Nanyang Technological University, Singapore, Singapore.; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore.; A*STAR ID Labs, Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore.; Laboratory for Translational and Molecular Imaging, Cancer and Stem Cell Biology Programme, Duke-NUS Medical School, Singapore, Singapore.; Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Department of Parasitology and Entomology, Faculty of Public Health, Mahidol University, Bangkok, Thailand.; Pillar of Engineering Product Development, Singapore University of Technology & Design, Singapore, Singapore.; Department of Reproductive Medicine, KK Women's and Children's Hospital, Singapore, Singapore.; Experimental Fetal Medicine Group, Department of Obstetrics and Gynecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.; Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia.; Université de Paris, UMR_S1134, BIGR, INSERM, Paris, France.; Institut National de Transfusion Sanguine, Paris, France.; Bioinformatics Institute, Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore.; Department of Biological Sciences, National University of Singapore, Singapore, Singapore.; CEA-Université Paris Sud 11-INSERM U1184, Immunology of Viral Infections and Autoimmune Diseases (IMVA-HB), IDMIT Department, IBFJ, DRF, Fontenay-aux-Roses, France.; Academic Clinical Program in Obstetrics and Gynecology, Duke-NUS Medical School, Singapore, Singapore.; Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.; Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, UK.; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore. [email protected].; A*STAR ID Labs, Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore. [email protected].; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore. [email protected].

DOI: 10.1038/s41564-021-00939-3

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MeSH Terms: Antigens, CD, Antigens, Protozoan, Erythrocytes, Fusion Regulatory Protein 1, Heavy Chain, Host-Parasite Interactions, Humans, Malaria, Vivax, Plasmodium vivax, Protein Binding, Protozoan Proteins, Receptors, Cell Surface, Receptors, Transferrin, Reticulocytes