Molecular interactions governing host-specificity of blood stage malaria parasites.

Non-human primates harbor diverse species of malaria parasites, including the progenitors of Plasmodium falciparum and Plasmodium vivax. Cross-species transmission of some malaria parasites-most notably the macaque parasite, Plasmodium 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.