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Review
. 2018 Dec:46:109-115.
doi: 10.1016/j.mib.201810002. Epub 2018 Oct 23.

Molecular and cellular interactions defining the tropism of Plasmodium vivax for reticulocytes

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Review

Molecular and cellular interactions defining the tropism of Plasmodium vivax for reticulocytes

Usheer Kanjee et al. Curr Opin Microbiol. 2018 Dec.

Abstract

Plasmodium vivax is uniquely restricted to invading reticulocytes, the youngest of red blood cells. Parasite invasion relies on the sequential deployment of multiple parasite invasion ligands. Correct targeting of the host reticulocyte is mediated by two families of invasion ligands: the reticulocyte binding proteins (RBPs) and erythrocyte binding proteins (EBPs). The Duffy receptor has long been established as a key determinant for P. vivax invasion. However, recently, the RBP protein PvRBP2b has been shown to bind to transferrin receptor, which is expressed on reticulocytes but lost on normocytes, implicating the ligand-receptor in the reticulocyte tropism of P. vivax. Furthermore there is increasing evidence for P. vivax growth and sexual development in reticulocyte-enriched tissues such as the bone marrow.

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Figures

Figure 1
Figure 1
P. vivax invasion of host cells. (A) Schematic showing the different steps during merozoite invasion of host RBC from initial weak attachment, reorientation, tight junction formation and invasion. (B) List of known and hypothesized P. vivax parasite invasion ligands along with summary reports of RBC binding, either directly or from orthologues, localization data to merozoite surface, rhoptry or microneme organelles and reactivity with patient sera.
Figure 2
Figure 2
Reticulocyte maturation and susceptibility to parasite invasion. CD34+ hematopoietic stem cells (HSCs) mature in the bone marrow lumen to form orthochromatic erythroblasts. These cells undergo a process of enucleation, producing a nascent reticulocyte and a pyrenocyte. Reticulocytes continue to mature initially in the bone marrow and subsequently in the peripheral circulation, eventually forming mature RBCs. Schematic levels of transferrin receptor (TfR) and susceptibility of cells to P. vivax and P. falciparum is indicated.

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