Research Article

Transferrin receptor 1 is a reticulocyte-specific receptor for Plasmodium vivax

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Science  05 Jan 2018:
Vol. 359, Issue 6371, pp. 48-55
DOI: 10.1126/science.aan1078

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Vivax malaria host receptor

Human malaria is caused by half a dozen species of Plasmodium protozoan parasites, each with distinctive biology. P. vivax, which causes relapsing malaria, specifically parasitizes immature red blood cells called reticulocytes. Gruszczyk et al. identified TfR1 (host transferrin receptor 1) as an alternative receptor for P. vivax. TfR1 binds to a specific P. vivax surface protein. However, the parasite that causes cerebral malaria, P. falciparum, does not share TfR1 as a receptor: P. falciparum could still infect cells in which TfR1 expression was knocked down, but P. vivax could not. Monoclonal antibodies to the P. vivax protein successfully hindered P. vivax infection of red blood cells.

Science, this issue p. 48

Abstract

Plasmodium 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.

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