Population genetic structure, genotypic and antigenic diversity of Theileria parva field strains from eastern and southern Africa

Abstract

Theileria parva utilizes genetic diversity as a survival strategy in evasion of the host’s immune system. Hence, effective control of T. parva infections is highly reliant on understanding the extent of genotypic and antigenic diversity of T. parva in cattle-derived and buffalo-derived isolates. Thus, the aim of this study was to identify differences between cattle- and buffalo-derived T. parva field parasites from eastern and southern Africa based on antigenic and genotypic diversity, and define the population genetic structure of T. parva parasites from the two regions. Sequence analysis of the central variable region of the sporozoite antigen gene, p67, revealed two subtypes of p67 allele type 1, an allele type previously exclusively associated with East Coast fever. Each subtype was unique to parasites from eastern and southern Africa, thus differentiating the p67 allele type 1 population responsible for Corridor disease in South Africa from that which occurs in East Africa. The other three p67 allele types (2, 3 and 4) were detected only from buffalo-derived T. parva parasites from buffalo and Corridor disease cases. Sequences of regions containing CD8+ T-cell epitopes in ten schizont antigens, designated Tp1 to Tp10, showed epitope variants in Tp1, Tp2, Tp4, Tp5 and Tp9, where Tp2 and Tp5 had the most and least variants respectively. Tp1, Tp2 and Tp9 had variants that were common in cattle- and buffalo-derived parasites from the two regions investigated. Variants on the immunodominant Tp249-59 and Tp250-59 epitopes were only identified in buffalo-derived parasites from South Africa, while one variant of Tp1214-224 was common in parasites from the two regions. The significance of Tp4 and Tp5 in immunity is not known and the effects of natural variants of Tp9 epitope on CTL recognition have not been reported. MS19 and ms5 loci were the most and least diverse respectively, and buffalo-derived T. parva parasites showed high levels of genetic diversity. Parasites associated with Corridor disease in South Africa and East Coast fever in eastern Africa had distinguishing allelic profiles on three loci (MS8, MS19 and MS33). Individual populations from the two regions were in linkage equilibrium (VD<L), however, when considered as one combined population, linkage disequilibrium (VD_L) was observed. The population structure of T. parva depicts a non-structured population with limited genetic intermixing between than within subpopulations, but with a close genetic relationship among cattle- and buffalo-derived T. parva parasites. Collectively, findings in this study show two subpopulations of T. parva that have adapted and are circulating in the two regions of Africa. Although some genotypes or alleles were exclusively detected in specific regions, it is possible that they could be underrepresented in the other region; hence, were not detected. The findings from analysis of the schizont antigens suggest that Tp1 and Tp2 could be better vaccine candidates compared to p67, in protection against a challenge with both cattle- and buffalo-derived T. parva parasites. The unique MS8, MS19 and MS33 profiles can be explored as possible markers for differentiation of ECF and Corridor disease parasites.