Molecular interactions governing host-specificity of blood stage malaria parasites

Abstract

Non-human primates harbor diverse species of malaria parasites, including the progenitors of P. falciparum and P. vivax. Cross-species transmission of some malaria parasites—most notably the macaque parasite, P. knowlesi—continues to this day, compelling the scientific community to ask whether these zoonoses could impede malaria control efforts by acting as a source of recurrent human infection. Host-restriction varies considerably among parasite species and is governed by both ecological and molecular variables. In particular, the efficiency of red blood cell invasion constitutes a prominent barrier to zoonotic emergence. Although proteins expressed upon the erythrocyte surface exhibit considerable diversity both within and among hosts, malaria parasites have adapted to this heterogeneity via the expansion of protein families associated with invasion, offering redundant mechanisms of host cell entry. This molecular toolkit may enable some parasites to circumvent host barriers, potentially yielding host shifts upon subsequent adaptation. Recent studies have begun to elucidate the molecular determinants of host-specificity, as well as the mechanisms that malaria parasites use to overcome these restrictions. We review recent studies concerning host tropism in the context of erythrocyte invasion by focusing on three malaria parasites that span the zoonotic spectrum: P. falciparum, P. knowlesi, and P. vivax.

Plasmodium yoelii Erythrocyte-Binding-like Protein Modulates Host Cell Membrane Structure, Immunity, and Disease Severity

“…Previous studies on EBL proteins in malaria parasites have focused on their roles in RBC invasion (1,(33)(34)(35). Our present study shows that PyEBL also modulates host recognition of iRBCs and immune responses through interaction with RBC membrane molecules, such as band 3 and PS, demonstrating a previously unrecognized mechanism of host-parasite interaction mediated by PyEBL (Fig.…”

Evolutionary history of humanPlasmodium vivaxrevealed by genome-wide analyses of related ape parasites

“…Adaptation of Plasmodium parasites to new host species has been associated with gains and losses of genes encoding proteins involved in red blood cell invasion ( 13 ). We therefore compared the repertoire of P. vivax invasion genes in the genomes of human and chimpanzee parasites.…”

“…Variation in the complement of RBPs is thought to influence the ability of Plasmodium parasites to invade erythrocytes ( 13 , 32 ). Human P. vivax , which exclusively invades reticulocytes, has full-length ORFs for five rbp genes ( rbp1a , rbp1b , rbp2a , rbp2b , and rbp2c ), all of which were conserved in the two chimpanzee P. vivax genomes PvSY56 and PvSY43.…”

“…Understanding the origin of human P. vivax and its relationship to the ape parasites is important for several reasons. First, only six Plasmodium species, out of several hundred so far described as infecting vertebrate hosts ( 12 ), have successfully colonized humans ( 13 ). Thus, the circumstances that surround the emergence of each of these human pathogens are of interest, especially since most, if not all, have nonhuman primate parasites as their closest relatives ( 7 , 9 , 14 ).…”

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“…[1,2] There are five species of Plasmodium which can cause malaria -Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, Plasmodium malariae, and Plasmodium knowlesi. [7] The dominant species responsible for causing malaria in humans is P. falciparum. The incidences of malaria caused by P. knowlesi in humans are sporadic.…”