A Novel Erythrocyte Binding Protein of Plasmodium vivax Suggests an Alternate Invasion Pathway into Duffy-Positive Reticulocytes.

Francis B Ntumngia,Luzia H Carvalho,Letícia De Menezes Torres,Richard Thomson-Luque,John H Adams,Karthigayan Gunalan,Louis H Miller

doi:10.1128/mbio.01261-16

Abstract

ABSTRACTErythrocyte invasion by malaria parasites is essential for blood-stage development and an important determinant of host range. In Plasmodium vivax, the interaction between the Duffy binding protein (DBP) and its cognate receptor, the Duffy antigen receptor for chemokines (DARC), on human erythrocytes is central to blood-stage infection. Contrary to this established pathway of invasion, there is growing evidence of P. vivax infections occurring in Duffy blood group-negative individuals, suggesting that the parasite might have gained an alternative pathway to infect this group of individuals. Supporting this concept, a second distinct erythrocyte binding protein (EBP2), representing a new member of the DBP family, was discovered in P. vivax and may be the ligand in an alternate invasion pathway. Our study characterizes this novel ligand and determines its potential role in reticulocyte invasion by P. vivax merozoites. EBP2 binds preferentially to young (CD71high) Duffy-positive (Fy+) reticulocytes and has minimal binding capacity for Duffy-negative reticulocytes. Importantly, EBP2 is antigenically distinct from DBP and cannot be functionally inhibited by anti-DBP antibodies. Consequently, our results do not support EBP2 as a ligand for invasion of Duffy-negative blood cells, but instead, EBP2 may represent a novel ligand for an alternate invasion pathway of Duffy-positive reticulocytes.

Highlights

Erythrocyte invasion by malaria parasites is essential for blood-stage development and an important determinant of host range
Unlike Plasmodium falciparum malaria, P. vivax blood-stage infection is limited to reticulocytes and individuals who are positive for the Duffy blood group antigen (Fy), known as the Duffy antigen receptor for chemokines (DARC) [3, 4]
Plasmodium vivax has the distinctive characteristic of invading reticulocytes, with a particular preference for reticulocytes expressing the surface Duffy blood group antigen, and P. vivax malaria is rare in populations with high Duffy negativity [3, 4, 7]

Summary

Introduction

Erythrocyte invasion by malaria parasites is essential for blood-stage development and an important determinant of host range. Preference for this blood cell type is believed to be mediated by specific ligand-receptor interactions between the parasite merozoites and the host reticulocytes during the invasion process [5, 6]. It is believed that the P. vivax Duffy binding protein (DBP) on the merozoite interacts with DARC on the reticulocyte surface, precipitating the junction formation step necessary for invasion.

Results

Conclusion