Trypanosoma brucei is exposed to the adaptive immune system and complement in the blood of its mammalian hosts. The aim of this review is to analyse the role and regulation of the proteins present on the external face of the plasma membrane in the long-term persistence of an infection and transmission. In particular, the following are addressed: (1) antigenic variation of the variant surface glycoprotein (VSG), (2) the formation of an effective VSG barrier shielding invariant surface proteins, and (3) the rapid uptake of VSG antibody complexes combined with degradation of the immunoglobulin and recycling of the VSG.
"Indeed, to evade population clearance despite constant exposure to the host adaptive immune system, they have evolved a unique surface. This includes a layer of the variant surface glycoprotein (VSG) that coats the entire cell surface providing protection to other proteins.8 Within this coat operate important nutrient receptors and surface proteins with a role in avoiding the toxic effects of innate immune factors.9 "
[Show abstract][Hide abstract] ABSTRACT: Trypanosoma and Plasmodium species are unicellular, eukaryotic pathogens that have evolved the capacity to survive and proliferate within a human host, causing sleeping sickness and malaria respectively. They have very different survival strategies. African trypanosomes divide in blood and extracellular spaces, whereas Plasmodium species invade and proliferate within host cells. Interaction with host macromolecules is central to establishment and maintenance of an infection by both parasites. Proteins that mediate these interactions are under selection pressure to bind host ligands without compromising immune avoidance strategies. In both parasites, the expansion of genes encoding a small number of protein folds has established large protein families. This has permitted both diversification to form novel ligand binding sites and variation in sequence that contributes to avoidance of immune recognition. In this review we consider two such parasite surface protein families, one from each species. In each case, known structures demonstrate how extensive sequence variation around a conserved molecular architecture provides an adaptable protein scaffold that the parasites can mobilise to mediate interactions with their hosts.
Protein Science 04/2014; 23(4). DOI:10.1002/pro.2428 · 2.85 Impact Factor
"In some forms of the parasite found in the host, the dense surface coat, composed mainly of a homogeneous layer of the parasite's variable surface protein, triggers an efficient antibody response. The continuous and complete replacement of these molecules by another immunologically distinct variable surface protein leads to prolonged infection (Prucca and Lujan 2009; Schwede and Carrington 2010; Tembo and Montgomery 2010; Recker et al. 2011). Here, we observed that VSG, VSP, and VAR are significantly enriched with repeats compared with the proteomes (fig. "
"Trypanosomes live extracellularly in the blood, exposed to several immune mechanisms.4,5 Their variant surface glycoprotein (VSG) forms a dense coat that thwarts innate immunity and prevents antibodies accessing invariant cell surface molecules and eliminating the infection.6 A key event in the evolution of VSGs appears to have been dispensing with specific biochemical function, allowing their sequence to vary enormously, with merely some general structural and processing constraints. "
[Show abstract][Hide abstract] ABSTRACT: The strategy of antigenic variation is to present a constantly changing population phenotype that enhances parasite transmission, through evasion of immunity arising within, or existing between, host animals. Trypanosome antigenic variation occurs through spontaneous switching among members of a silent archive of many hundreds of variant surface glycoprotein (VSG) antigen genes. As with such contingency systems in other pathogens, switching appears to be triggered through inherently unstable DNA sequences. The archive occupies subtelomeres, a genome partition that promotes hypermutagenesis and, through telomere position effects, singular expression of VSG. Trypanosome antigenic variation is augmented greatly by the formation of mosaic genes from segments of pseudo-VSG, an example of implicit genetic information. Hypermutation occurs apparently evenly across the whole archive, without direct selection on individual VSG, demonstrating second-order selection of the underlying mechanisms. Coordination of antigenic variation, and thereby transmission, occurs through networking of trypanosome traits expressed at different scales from molecules to host populations.
Annals of the New York Academy of Sciences 09/2012; 1267(1):11-7. DOI:10.1111/j.1749-6632.2012.06654.x · 4.38 Impact Factor
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