Erythrocyte Invasion Mechanisms in Plasmodium vivax Malaria

Erythrocyte invasion by Plasmodium vivax merozoites is a highly orchestrated, multistep process that underpins blood-stage infection and disease pathology. Following egress from the liver, free merozoites recognise and attach to circulating reticulocytes via specialised ligand–receptor interactions. The primary pathway employs the parasite Duffy-binding protein (DBP) to engage the Duffy antigen receptor for chemokines (DARC) on reticulocyte surfaces, triggering conformational changes that enable tight-junction formation and internalisation. A distinct family of reticulocyte-binding proteins (PvRBPs) further refines host-cell tropism by targeting immature red blood cells. Recent findings also support the presence of an alternative DBP paralogue that may mediate secondary invasion routes in Duffy-positive cells. Sequential ligand engagement, merozoite reorientation and moving-junction assembly culminate in parasite entry within a parasitophorous vacuole. A detailed understanding of each molecular step is essential for rational design of vaccines and inhibitors aimed at blocking invasion and reducing the global burden of vivax malaria.

Research from Nature Portfolio

Recent studies have elucidated the sequential roles of binding families in invasion using a related malaria model. By employing precise genome editing in Plasmodium knowlesi, researchers demonstrated that a single Duffy-binding protein (DBPα) and a reticulocyte-binding-like ligand (NBPXa) act in distinct, ordered phases immediately prior to erythrocyte entry. These experiments defined key invasion milestones, confirmed non-redundant functions for each ligand family and revealed that simultaneous targeting of both molecules with inhibitory antibodies can synergistically block host-cell engagement. This phased commitment model refines our conception of merozoite invasion and highlights new opportunities for combination therapies.

Erythrocyte Invasion Mechanisms in Plasmodium vivax Malaria publication trend

The graph below shows the total number of articles in erythrocyte invasion mechanisms in plasmodium vivax malaria across all publications each year (not limited to Nature Index journals).

Technical terms

Merozoite: The invasive, blood-stage form of the malaria parasite that attaches to and enters erythrocytes.

Reticulocyte: An immature red blood cell that retains surface receptors exploited by P. vivax for selective invasion.

Duffy antigen receptor for chemokines (DARC): A surface protein on reticulocytes serving as the canonical receptor for P. vivax DBP binding.

Duffy-binding protein (DBP): A parasite ligand that recognises and binds DARC to mediate tight-junction assembly and erythrocyte entry.

Reticulocyte-binding protein (PvRBP): A family of parasite ligands that determine host-cell tropism by binding distinct erythrocyte or reticulocyte receptors.

References

1. Sequential roles for red blood cell binding proteins enable phased commitment to invasion for malaria parasites. Nature Communications (2023).
2. Red Blood Cell Invasion by Plasmodium vivax: Structural Basis for DBP Engagement of DARC. PLOS Pathogens (2014).
3. A Novel Erythrocyte Binding Protein of Plasmodium vivax Suggests an Alternate Invasion Pathway into Duffy-Positive Reticulocytes. mBio (2016).
4. Plasmodium vivax Reticulocyte Binding Proteins Are Key Targets of Naturally Acquired Immunity in Young Papua New Guinean Children. PLOS Neglected Tropical Diseases (2016).