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Plasmodium simium  is a parasite from New World monkeys that is most closely related to the human malaria parasite  Plasmodium vivax ; it also naturally infects humans. The blood-stage infection of  P .  vivax  depends on Duffy binding protein II (PvDBPII) and its cognate receptor on erythrocytes, the Duffy antigen receptor for chemokines (hDARC), but there is no information on the  P .  simium  erythrocytic invasion pathway. The genes encoding  P .  simium  DBP (PsDBP II ) and simian DARC (sDARC) were sequenced from Southern brown howler monkeys ( Alouatta guariba clamitans ) naturally infected with  P .  simium  because  P .  simium  may also depend on the DBPII/DARC interaction. The sequences of DBP binding domains from  P .  vivax  and  P .  simium  were highly similar. However, the genetic variability of PsDBPII was lower than that of PvDBPII. Phylogenetic analyses demonstrated that these genes were strictly related and clustered in the same clade of the evolutionary tree. DARC from  A .  clamitans  was also sequenced and contained three new non-synonymous substitutions. None of these substitutions were located in the N-terminal domain of DARC, which interacts directly with DBPII. The interaction between sDARC and PvDBPII was evaluated using a cytoadherence assay of COS7 cells expressing PvDBPII on their surfaces. Inhibitory binding assays  in vitro  demonstrated that antibodies from monkey sera blocked the interaction between COS-7 cells expressing PvDBPII and hDARC-positive erythrocytes. Taken together, phylogenetic analyses reinforced the hypothesis that the host switch from humans to monkeys may have occurred very recently in evolution, which sheds light on the evolutionary history of new world plasmodia. Further invasion studies would confirm whether  P .  simium  depends on DBP/DARC to trigger internalization into red blood cells.

plos one

Plasmodium simium, a Plasmodium vivax-Related Malaria Parasite: Genetic Variability of Duffy Binding Protein II and the Duffy Antigen/Receptor for Chemokines