Evolution and diversity of the EMA families of the divergent equid parasites, Theileria equi and T. haneyi

Authors: WISE, LAUREN - Washington State University; Kappmeyer, Lowell; KNOWLES, DONALD - Washington State University; White, Stephen

Submitted to: Infection, Genetics and Evolution
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/17/2018
Publication Date: 3/1/2019
Citation: Wise, L.N., Kappmeyer, L.S., Knowles, D.P., White, S.N. 2019. Evolution and diversity of the EMA families of the divergent equid parasites, Theileria equi and T. haneyi. Infection, Genetics and Evolution. 68:153-160. https://doi.org/10.1016/j.meegid.2018.12.020.
DOI: https://doi.org/10.1016/j.meegid.2018.12.020

Interpretive Summary: The equine parasite Theileria equi causes piroplasmosis in horses and other equids, and control of piroplasmosis severely restricts equine movements for sporting events and other forms of economic activity. A recently discovered parasite related to T. equi, Theileria haneyi, also infects equids and can serve as an infectious reservoir. These two divergent parasites share a unique gene family that express cell surface proteins termed EMA proteins. This protein family is unique to Theileria species, which usually have only one EMA gene each. However, both T. equi and T. haneyi have 9 EMA genes despite diverging as separate species over 30 million years ago. A detailed scan of these EMA genes revealed no signatures of historical diversifying selection, indicating they do not function to help evade the immune system directly, but rather serve in host adaptation and persistence. Biochemical analysis revealed the presence of a conserved protein domain with some similarity to the hemolysin toxin found in cobra venom. This finding combined with data from protein interaction prediction models may indicate roles in entering or exiting host cells during infection. Overall, these findings clarify the roles of EMA gene family genes in Theileria parasites of equine hosts, and they provide a useful step forward for additional research to minimize economic damage from equine piroplasmosis.

Technical Abstract: The equine parasite Theilera equi continues to curtail global equine commerce due primarily to its ability to persist indefinitely in the immunocompetent horse. Details regarding the parasite life cycle, pathogenesis and mechanism of persistence remain unclear. The recently discovered T. haneyi is also capable of persistence in the horse, creating a potential reservoir for additional infections. These two divergent parasites share a unique gene family that expresses surface merozoite antigens, or equi merozoite antigens (EMAs). The EMA family was maintained in number and size in both parasites despite a species divergence of over 30 million years ago. This family is unique amongst Theilerias in number, structure and biochemical properties. In silico analysis revealed no evidence of selection for diversity within this family, indicating a role in host adaptation and persistence rather than antigenic variation and immune escape. Biochemical analysis revealed the presence of a conserved domain, homologous to the hemolysin toxin found in cobra venom. This finding combined with data from protein interaction prediction models may indicate interaction with the structural components of the host erythrocyte and a role in merozoite entry or escape. Additional predicted protein interactions focus on disruption of the enzymatic functions of the host cell, potentially resulting in enhanced parasite survival.