Title : PVX_112690 (PvTRAg36.6) - CD71/TFRC interaction study - new insight of plasmodium vivax invasion into human reticulocyte

Abstract:

Aligned with the global objective to eliminate malaria, continuous efforts are made in the field of malaria biology. However, the parasite is similarly advancing itself to be in competition. Our information about parasites is the tip of the iceberg, making this tug of war into the parasite side. Molecular mechanisms of host-parasite interaction during malaria remain elusive, especially in the case of Plasmodium vivax. Duffy antigen was the only known receptor for P. vivax invasion for a long time till long. However, alternative pathways of invasion are now coming up. P. vivax has a specific gene family named Pv-fam-a that encodes a large number of tryptophan-rich antigens (PvTRAgs). Several PvTRAgs bind to host erythrocytes, but identifying their host receptors requires further investigation.

We describe here the identification of erythrocyte receptors for one of the significant P. vivax tryptophan-rich antigens, PvTRAg36.6 which is known to be expressed in merozoites, has its sequences conserved in the parasite population, and produces cellular and humoral immune responses during P. vivax infection. PvTRAg36.6 binds to the human reticulocytes, with the reticulocyte specific receptor, CD71, based on LC-MS analysis of proteins obtained during pull down assay. This receptor-ligand interaction was specific as confirmed by direct binding between PvTRAg36.6 and CD71 during solid-phase binding, and Surface Plasmon Resonance assays.

Furthermore, the eukaryotic expression systems; yeast-two-hybrid system, and Rosetting of erythrocytes around mammalian HEK cell expressing PvTRAg36.6 on its surface, also confirmed this receptor-ligand interaction. In this study we found out that the parasite ligand PvTRAg36.6 interacts with its reticulocyte receptor CD71 through its two peptide regions, and is involved in red cell invasion. These results may help in developing the immuno- therapeutics against this parasitic infection.

Audience Take Away:

• Insight about invasion of P. vivax Invasion into human reticulocyte.
• This will help to develop therapeutics against P. vivax malaria.
• This information can be used to develop vaccine against P. vivax malaria

Biography:

Manish Tripathi completed his post-graduation from AIIMS, New Delhi (2018) and did his dissertation from Molecular Parasitology Lab on the subject ‘To identify the complex forming Plasmodium vivax Tryptophan-Rich Antigens’. He is currently a Ph.D. schola. His research is focused on the characterization of parasite ligand- host receptor interaction in Plasmodium infection using proteomics-based approach, in-silico techniques, and Plasmodium vivax culture.