Jakub GruszczykUsheer KanjeeLi Jin ChanSébastien MenantBenoit MalleretNicholas T.Y. LimChristoph Q. SchmidtYee Foong MokKai Min LinRichard D. PearsonGabriel RangelBrian J. SmithMelissa J. CallMichael P. WeekesMichael D.W. GriffinJames M. MurphyJonathan AbrahamKanlaya SriprawatMaria J. MenezesMarcelo U. FerreiraBruce RussellLaurent ReniaManoj T. DuraisinghWai Hong ThamA-Star, Singapore Immunology NetworkCambridge Institute for Medical ResearchHarvard School of Public HealthWalter and Eliza Hall Institute of Medical ResearchYong Loo Lin School of MedicineUniversity of MelbourneUniversity of OtagoMahidol UniversityUniversität UlmUniversidade de Sao Paulo - USPLa Trobe UniversityWellcome Sanger InstituteHarvard Medical SchoolLi Ka Shing Centre for Health Information and Discovery2019-08-282019-08-282018-01-05Science. Vol.359, No.6371 (2018), 48-5510959203003680752-s2.0-85040101798https://repository.li.mahidol.ac.th/handle/20.500.14594/47538Plasmodium vivax shows a strict host tropism for reticulocytes.We identified transferrin receptor 1 (TfR1) as the receptor for P. vivax reticulocyte-binding protein 2b (PvRBP2b).We determined the structure of the N-terminal domain of PvRBP2b involved in red blood cell binding, elucidating the molecular basis for TfR1 recognition.We validated TfR1 as the biological target of PvRBP2b engagement by means of TfR1 expression knockdown analysis. TfR1 mutant cells deficient in PvRBP2b binding were refractory to invasion of P. vivax but not to invasion of P. falciparum. Using Brazilian and Thai clinical isolates, we show that PvRBP2b monoclonal antibodies that inhibit reticulocyte binding also block P. vivax entry into reticulocytes.These data show that TfR1-PvRBP2b invasion pathway is critical for the recognition of reticulocytes during P. vivax invasion.Mahidol UniversityMultidisciplinaryArticleSCOPUS10.1126/science.aan1078