Transcriptome profiling of <i>Plasmodium vivax</i> in <i>Saimiri</i> monkeys identifies potential ligands for invasion.

Abstract

Unlike the case in Asia and Latin America, <i>Plasmodium vivax</i> 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 <i>P. vivax</i> merozoite invasion ligand, Duffy binding protein 1 (DBP1). However, <i>P. vivax</i> infections have been documented in Duffy-negative individuals throughout Africa, suggesting that <i>P. vivax</i> may use ligands other than DBP1 to invade Duffy-negative erythrocytes through other receptors. To identify potential <i>P. vivax</i> ligands, we compared parasite gene expression in <i>Saimiri</i> and <i>Aotus</i> monkey erythrocytes infected with <i>P. vivax</i> Salvador I (Sal I). DBP1 binds <i>Aotus</i> but does not bind to <i>Saimiri</i> erythrocytes; thus, <i>P. vivax</i> Sal I must invade <i>Saimiri</i> erythrocytes independent of DBP1. Comparing RNA sequencing (RNAseq) data for late-stage infections in <i>Saimiri</i> and <i>Aotus</i> 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 <i>Saimiri</i> infections compared with <i>Aotus</i> infections. These genes may encode potential ligands responsible for <i>P. vivax</i> infections of Duffy-negative Africans.