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<jats:p><jats:italic>Plasmodium vivax</jats:italic> shows a strict host tropism for reticulocytes. We identified transferrin receptor 1 (TfR1) as the receptor for <jats:italic>P. vivax</jats:italic> 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 <jats:italic>P. vivax</jats:italic> but not to invasion of <jats:italic>P. falciparum</jats:italic>. Using Brazilian and Thai clinical isolates, we show that PvRBP2b monoclonal antibodies that inhibit reticulocyte binding also block <jats:italic>P. vivax</jats:italic> entry into reticulocytes. These data show that TfR1-PvRBP2b invasion pathway is critical for the recognition of reticulocytes during <jats:italic>P. vivax</jats:italic> invasion.</jats:p>

Original publication

DOI

10.1126/science.aan1078

Type

Journal article

Journal

Science

Publisher

American Association for the Advancement of Science (AAAS)

Publication Date

05/01/2018

Volume

359

Pages

48 - 55