Variant antigen diversity inTrypanosoma vivaxis not driven by recombination

Abstract

African trypanosomes are vector-borne haemoparasites that cause African trypanosomiasis in humans and animals. Parasite survival in the bloodstream depends on immune evasion, achieved by antigenic variation of the Variant Surface Glycoprotein (VSG) coating the trypanosome cell surface. Recombination, or rather directed gene conversion, is fundamental inTrypanosoma brucei, as both a mechanism ofVSGgene switching and of generating antigenic diversity during infections.Trypanosoma vivaxis a related, livestock pathogen also displaying antigenic variation, but whoseVSGlack key structures necessary for gene conversion inT. brucei. Thus, this study tests a long-standing prediction thatT. vivaxhas a more restricted antigenic repertoire. Here we show that globalVSGrepertoire is broadly conserved across diverseT. vivaxclinical strains. We use sequence mapping, coalescent approaches and experimental infections to show that recombination plays little, if any, role in diversifyingT. vivax VSGsequences. These results explain interspecific differences in disease, such as propensity for self-cure, and indicate that eitherT. vivaxhas an alternate mechanism for immune evasion or else a distinct transmission strategy that reduces its reliance on long-term persistence. The lack of recombination driving antigenic diversity inT. vivaxhas immediate consequences for both the current mechanistic model of antigenic variation in African trypanosomes and species differences in virulence and transmission strategy, requiring us to reconsider the wider epidemiology of animal African trypanosomiasis.