Abstract
African trypanosomes escape the mammalian immune response by antigenic variation—the periodic exchange of one surface coat protein, in Trypanosoma brucei the variant surface glycoprotein (VSG), for an immunologically distinct one. VSG transcription is monoallelic, with only one VSG being expressed at a time from a specialized locus, known as an expression site. VSG switching is a predominantly recombination-driven process that allows VSG sequences to be recombined into the active expression site either replacing the currently active VSG or generating a ‘new’ VSG by segmental gene conversion. In this review, we describe what is known about the factors that influence this process, focusing specifically on DNA repair and recombination.
Highlights
Pathogens have evolved to survive in environments that are often hostile to them
The vector-borne protozoan parasite T. brucei is the causative agent of human African trypanosomiasis (HAT) and animal African trypanosomiasis (AAT), and remains today a pervasive public health issue in sub-Saharan Africa
Between African trypanosome species, which include T. b. gambiense, T. b. rhodesiense, T. equiperdum, T. congolense and T. vivax, antigenic variation is commonly used but variant surface glycoprotein (VSG) gene diversity is dictated by the scale of recombination within each species, at least for T. b. brucei, T. congolense and T. vivax [5]
Summary
Pathogens have evolved to survive in environments that are often hostile to them. Common to several, including protozoan parasites, bacterial and fungal species, is escape of the host immune response by antigenic variation, the periodic exchange of one antigen for an immunologically distinct one. A massive expansion of VSG genes has resulted in approximately 2000 genes and pseudogenes being dedicated to this gene family This is between one and two orders of magnitude larger than other pathogens that use antigenic variation as an immune evasion mechanism. This expansion is probably due to selective pressure exerted upon trypanosomes to maintain antigen diversity. Trypanosome infections were previously thought to be confined to the blood and cerebrospinal fluid, but parasites have been detected in the skin of asymptomatic patients who were negative for the presence of parasites in the blood [6], and have been shown to reside in the adipose tissue of rodent models [7] Both HAT and AAT are potentially fatal and treatment of the disease may be further complicated by the tropism of the parasite. We will describe the VSG genomic environment, the mechanisms of VSG switching, DNA double-strand break as a trigger for VSG switching, how chromatin components influence this process and future avenues for study of antigenic variation
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