Rosetting is a virulent Plasmodium falciparum phenomenon associated with severe malaria. Here we demonstrate that P. falciparum-encoded repetitive interspersed families of polypeptides (RIFINs) are expressed on the surface of infected red blood cells (iRBCs), where they bind to RBCs--preferentially of blood group A--to form large rosettes and mediate microvascular binding of iRBCs. We suggest that RIFINs have a fundamental role in the development of severe malaria and thereby contribute to the varying global distribution of ABO blood groups in the human population.

Background: Parasitic protozoans possess many multicopy gene families which have central roles in parasite survival and virulence. The number and variability of members of these gene families often make it difficult to predict possible functions of the encoded proteins. The families of extracellular proteins that are exposed to a host immune response have been driven via immune selection to become antigenically variant, and thereby avoid immune recognition while maintaining protein function to establish a chronic infection.

Inhibition of the small GTPase ras homology protein (Rho) or its downstream target, the Rho-associated kinase (ROCK), has been shown to promote axon regeneration and to improve functional recovery following spinal cord injury (SCI) in the adult rat. Here, we have analyzed the expression of RhoA and RhoB following spinal cord injury in order to assess whether Rho is a possible target for late pharmacological intervention. In control spinal cords, RhoA(+) cells were almost absent, whereas RhoB was localized to some ependymal cells, a few microglia, and some dissociated neurons. In injured spinal cords, RhoA(+) and RhoB(+)cells accumulated at perilesional areas and in the developing necrotic core early after injury at day 1. After reaching their maximum levels (RhoA at day 3; RhoB at day 1), RhoA(+) and RhoB(+) cell numbers remained significantly elevated until day 28. In areas remote from the lesion (> or =0.75 mm), a more discrete accumulation of RhoA(+) and RhoB(+) cells was observed, primarily in areas of ongoing Wallerian degeneration. RhoA and RhoB were predominantly expressed by polymorphonuclear granulocytes, ED1(+) microglia/macrophages, oligodendrocytes, some neurons, and swollen axons/neurites. Furthermore, expression was located to lesional, reactive astrocytes and fibroblastoid cells confined to areas of scar formation. Our experiments have determined that most RhoA(+) and RhoB(+) cells (>70%) are of mononuclear origin. The persistent presence of lesional RhoA(+) and RhoB(+) axon/neurite fibers over a period of 4 weeks after injury suggests that Rho inhibition is a putative therapeutic concept also for delayed intervention after SCI.