Transcriptome profiling of Plasmodium vivax in Saimiri monkeys identifies potential ligands for invasion

Proc Natl Acad Sci U S A. 2019 Apr 2;116(14):7053-7061. doi: 10.1073/pnas.1818485116. Epub 2019 Mar 14.

Abstract

Unlike the case in Asia and Latin America, Plasmodium vivax infections are rare in sub-Saharan Africa due to the absence of the Duffy blood group antigen (Duffy antigen), the only known erythrocyte receptor for the P. vivax merozoite invasion ligand, Duffy binding protein 1 (DBP1). However, P. vivax infections have been documented in Duffy-negative individuals throughout Africa, suggesting that P. vivax may use ligands other than DBP1 to invade Duffy-negative erythrocytes through other receptors. To identify potential P. vivax ligands, we compared parasite gene expression in Saimiri and Aotus monkey erythrocytes infected with P. vivax Salvador I (Sal I). DBP1 binds Aotus but does not bind to Saimiri erythrocytes; thus, P. vivax Sal I must invade Saimiri erythrocytes independent of DBP1. Comparing RNA sequencing (RNAseq) data for late-stage infections in Saimiri and Aotus erythrocytes when invasion ligands are expressed, we identified genes that belong to tryptophan-rich antigen and merozoite surface protein 3 (MSP3) families that were more abundantly expressed in Saimiri infections compared with Aotus infections. These genes may encode potential ligands responsible for P. vivax infections of Duffy-negative Africans.

Keywords: Aotus; Duffy binding protein; Duffy blood group antigen; Plasmodium vivax; Saimiri.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Antigens, Protozoan / genetics
  • Antigens, Protozoan / metabolism*
  • Duffy Blood-Group System / genetics
  • Duffy Blood-Group System / metabolism*
  • Erythrocytes / metabolism
  • Erythrocytes / parasitology*
  • Gene Expression Profiling*
  • Malaria, Vivax / genetics
  • Malaria, Vivax / metabolism*
  • Plasmodium vivax / genetics
  • Plasmodium vivax / metabolism*
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism*
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Saimiri

Substances

  • Antigens, Protozoan
  • Duffy Blood-Group System
  • Duffy antigen binding protein, Plasmodium
  • Protozoan Proteins
  • Receptors, Cell Surface