Host-parasite interaction: selective Pv-fam-a family proteins of Plasmodium vivax bind to a restricted number of human erythrocyte receptors

J Infect Dis. 2015 Apr 1;211(7):1111-20. doi: 10.1093/infdis/jiu558. Epub 2014 Oct 13.

Abstract

Background: Plasmodium vivax synthesizes the largest number of 36 tryptophan-rich proteins belonging to the Pv-fam-a family. These parasite proteins need to be characterized for their biological function because tryptophan-rich proteins from other Plasmodium species have been proposed as vaccine candidates.

Methods: Recombinant P. vivax tryptophan-rich antigens (PvTRAgs) were used to determine their erythrocyte-binding activity by a cell-based enzyme-linked immunosorbent assay, flow cytometry, and a rosetting assay.

Results: Only 4 (PvTRAg26.3, PvTRAg34, PvTRAg36, and PvTRAg36.6) of 21 PvTRAgs bind to host erythrocytes. The cross-competition data indicated that PvTRAg36 and PvTRAg34 share their erythrocyte receptors with previously described proteins PvTRAg38 and PvTRAg33.5, respectively. On the other hand, PvTRAg26.3 and PvTRAg36.6 cross-compete with each other and not with any other PvTRAg, indicating that these 2 proteins bind to the same but yet another set of erythrocyte receptor(s). Together, 10 of 36 PvTRAgs possess erythrocyte-binding activity in which each protein recognizes >1 erythrocyte receptor. Further, each erythrocyte receptor is shared by >1 PvTRAg.

Conclusions: This redundancy may be useful for the parasite to invade red blood cells and cause disease pathogenesis, and it can be exploited to develop therapeutics against P. vivax malaria.

Keywords: host cell invasion; malaria parasite; receptor-ligand interaction; tryptophan-rich proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Protozoan / immunology
  • Antigens, Protozoan / genetics
  • Antigens, Protozoan / immunology
  • Antigens, Protozoan / metabolism*
  • Cell Line
  • Cricetulus
  • Enzyme-Linked Immunosorbent Assay
  • Erythrocytes / immunology
  • Erythrocytes / metabolism*
  • Erythrocytes / parasitology
  • Female
  • Genome, Protozoan / genetics
  • Host-Parasite Interactions*
  • Humans
  • Malaria, Vivax / blood
  • Malaria, Vivax / immunology
  • Malaria, Vivax / parasitology*
  • Plasmodium vivax / genetics
  • Plasmodium vivax / immunology
  • Plasmodium vivax / metabolism*
  • Protein Binding
  • Protozoan Proteins / genetics
  • Protozoan Proteins / immunology
  • Protozoan Proteins / metabolism*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • Recombinant Proteins / metabolism
  • Sequence Analysis, DNA
  • Tryptophan / metabolism

Substances

  • Antibodies, Protozoan
  • Antigens, Protozoan
  • Protozoan Proteins
  • Recombinant Proteins
  • Tryptophan