Comparative Transcriptomics of the Bovine Apicomplexan Parasite Theileria parva Developmental Stages Reveals Massive Gene Expression Variation and Potential Vaccine Antigens

Kodzo Atchou,Christian Tiambo,Roger Pelle,Joana C Silva,Juliette Ongus,John Juma,Appolinaire Djikeng,Eunice Machuka

doi:10.3389/fvets.2020.00287

Abstract

Theileria parva is a protozoan parasite that causes East Coast fever (ECF), an economically important disease of cattle in Africa. It is transmitted mainly by the tick Rhipicephalus appendiculatus. Research efforts to develop a subunit vaccine based on parasite neutralizing antibodies and cytotoxic T-lymphocytes have met with limited success. The molecular mechanisms underlying T. parva life cycle stages in the tick vector and bovine host are poorly understood, thus limiting progress toward an effective and efficient control of ECF. Transcriptomics has been used to identify candidate vaccine antigens or markers associated with virulence and disease pathology. Therefore, characterization of gene expression throughout the parasite's life cycle should shed light on host–pathogen interactions in ECF and identify genes underlying differences in parasite stages as well as potential, novel therapeutic targets. Recently, the first gene expression profiling of T. parva was conducted for the sporoblast, sporozoite, and schizont stages. The sporozoite is infective to cattle, whereas the schizont is the major pathogenic form of the parasite. The schizont can differentiate into piroplasm, which is infective to the tick vector. The present study was designed to extend the T. parva gene expression profiling to the piroplasm stage with reference to the schizont. Pairwise comparison revealed that 3,279 of a possible 4,084 protein coding genes were differentially expressed, with 1,623 (49%) genes upregulated and 1,656 (51%) downregulated in the piroplasm relative to the schizont. In addition, over 200 genes were stage-specific. In general, there were more molecular functions, biological processes, subcellular localizations, and pathways significantly enriched in the piroplasm than in the schizont. Using known antigens as benchmarks, we identified several new potential vaccine antigens, including TP04_0076 and TP04_0640, which were highly immunogenic in naturally T. parva-infected cattle. All the candidate vaccine antigens identified have yet to be investigated for their capacity to induce protective immune response against ECF.

Highlights

Cattle production constitutes a significant component of agriculture, economy, and food security in the world, especially in developing countries [1, 2]
The schizont reads mapped to transcripts of 3,891 genes, whereas reads from the piroplasm mapped to transcripts of 3,887 genes
4,061 different protein coding genes were identified by the combined schizont and piroplasm reads out of a possible 4,084 protein coding genes predicted by the recent re-annotation of the T. parva genome [44]

Summary

INTRODUCTION

Cattle production constitutes a significant component of agriculture, economy, and food security in the world, especially in developing countries [1, 2]. That first comparative transcriptomic analysis revealed that the development of the parasite from the sporozoite in the tick vector into the schizont in the bovine host cells is accompanied by a drastic increase of upregulated genes, though the 10 most highly expressed genes occurred in the arthropod stages. It identified several genes with expression similar to known candidate vaccine antigen genes and revealed errors in the structural annotation of the T. parva genome. Data from previous [16] and current studies were combined in our analysis for the search of new candidate vaccine antigens

Ethics Statements

RESULTS

DISCUSSION

ETHICS STATEMENT