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Science. 2018 Jan 5;359(6371):48-55. doi: 10.1126/science.aan1078.

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

Author information

1
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
2
Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.
3
Department of Medical Biology, The University of Melbourne, Melbourne, Victoria 3010, Australia.
4
Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, 117597 Singapore.
5
Singapore Immunology Network, A*STAR, 138648 Singapore.
6
Institute of Pharmacology of Natural Products and Clinical Pharmacology, Ulm University, Germany.
7
Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Victoria 3010, Australia.
8
Cambridge Institute for Medical Research, Cambridge CB2 OXY, UK.
9
Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
10
Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, Oxford, UK.
11
La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086, Australia.
12
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
13
Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.
14
Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
15
Department of Microbiology and Immunology, University of Otago, Dunedin 9054, New Zealand.

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.

PMID:
29302006
PMCID:
PMC5788258
DOI:
10.1126/science.aan1078
[Indexed for MEDLINE]
Free PMC Article

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