Elsevier

Infection, Genetics and Evolution

Volume 27, October 2014, Pages 250-263
Infection, Genetics and Evolution

Review
Evolution and genetic diversity of Theileria

https://doi.org/10.1016/j.meegid.2014.07.013Get rights and content

Highlights

  • Hosts and ticks are involved in Theileria evolution.

  • Genetic diversity is a survival strategy of Theileria.

  • Genetic recombination is the major mechanism underlying the diversity of Theileria.

  • Genetic diversity can sometimes be linked to the virulence and host specificity of Theileria.

  • Vaccine development against Theileria is constrained by the genetic diversity of this parasite.

Abstract

Theileria parasites infect a wide range of domestic and wild ruminants worldwide, causing diseases with varying degrees of severity. A broad classification, based on the parasite’s ability to transform the leukocytes of host animals, divides Theileria into two groups, consisting of transforming and non-transforming species. The evolution of transforming Theileria has been accompanied by drastic changes in its genetic makeup, such as acquisition or expansion of gene families, which are thought to play critical roles in the transformation of host cells. Genetic variation among Theileria parasites is sometimes linked with host specificity and virulence in the parasites. Immunity against Theileria parasites primarily involves cell-mediated immune responses in the host. Immunodominance and major histocompatibility complex class I phenotype-specificity result in a host immunity that is tightly focused and strain-specific. Immune escape in Theileria is facilitated by genetic diversity in its antigenic determinants, which potentially results in a loss of T cell receptor recognition in its host. In the recent past, several reviews have focused on genetic diversity in the transforming species, Theileria parva and Theileria annulata. In contrast, genetic diversity in Theileria orientalis, a benign non-transforming parasite, which occasionally causes disease outbreaks in cattle, has not been extensively examined. In this review, therefore, we provide an outline of the evolution of Theileria, which includes T. orientalis, and discuss the possible mechanisms generating genetic diversity among parasite populations. Additionally, we discuss the potential implications of a genetically diverse parasite population in the context of Theileria vaccine development.

Introduction

Theileria parasites infect a wide range of hosts, including domestic and wild ruminants, and often induce clinical disorders in the infected animals. Although several non-ruminant animals are also described as being hosts for Theileria parasites, such as Theileria youngi in woodrat (Kjemtrup et al., 2001), Theileria annae in fox (Camacho et al., 2001), and Theileria equi in horse (Mehlhorn and Schein, 1998), these species are considered to have evolved prior to Theileria species of ruminants (Criado-Fornelio et al., 2003). Theileria parasites can be broadly categorized into two groups, consisting of host-cell transforming and non-transforming species. Traditionally, the following species have been described as transforming Theileria: Theileria parva, Theileria annulata, Theileria lestoquardi, and Theileria taurotragi (Dobbelaere and Küenzi, 2004, Sugimoto and Fujisaki, 2002). However, the recent studies added Theileria sp. (buffalo), a benign Theileria parasite in African buffaloes, to the list of transforming parasite species (Chaisi et al., 2011, Zweygarth et al., 2009). Several species of non-transforming parasites exist, including Theileria orientalis, Theileria mutans, Theileria velifera, and Theileria cervi. This classification is based on the parasite’s ability to transform host leukocytes in a way that enables the infected cells to proliferate indefinitely along with the parasites occupying them. Non-transforming Theileria parasites do not induce this type of host-cell proliferation. Although the parasites in the latter category are considered to be relatively benign, disease outbreaks and economic losses related to the farm animals affected are not uncommon (Aparna et al., 2011, Eamens et al., 2013, McFadden et al., 2011). The taxonomy of the benign Theileria sergenti/buffeli/orientalis group is controversial. Arguments have been put forward both ways that these parasites should be classified as one species or as separate species within a group (Fujisaki et al., 1994, Gubbels et al., 2000a, Kakuda et al., 1998, Uilenberg et al., 1985). We have used the common taxonomic name, T. orientalis, throughout this review.

T. parva and T. annulata are both known to infect cattle (Bos Taurus/Bos indicus) and buffaloes (Syncerus caffer/Bubalus bubalis) (Bishop et al., 2004), while T. orientalis infects yaks (Bos grunniens) as well as cattle and buffaloes (B. bubalis) (Fujisaki et al., 1994, Yin et al., 2004). In addition, several Theileria species (T. lestoquardi, Theileria separata, Theileria uilenbergi, Theileria luwenshuni, Theileria capreoli, and Theileria ovis) have been reported to infect small ruminants (Ahmed et al., 2006). Wild ruminants, such as deer, antelope, and giraffe, are infected with several as yet unclassified Theileria parasites, some of which are highly pathogenic and often lead to death among these animals (Höfle et al., 2004, Nijhof et al., 2005, Oosthuizen et al., 2009).

The lifecycle of Theileria parasites in the ruminant host and tick vector has been reviewed (Bishop et al., 2004, Shaw and Tilney, 1992). Briefly, the lifecycle involves asexual reproduction of the blood-stage parasites in the host animal, and sexual reproduction of the parasites in a tick vector. The lifecycle in the vertebrate host begins with infection by sporozoites during blood-feeding of infected ticks. Thereafter, the sporozoites infect nucleated blood cells, where they may transform into schizonts. In the case of transforming Theileria, the infected cells (leukocytes) can multiply indefinitely in the host when they are harboring such parasites, and schizont-infected cells are often found in the circulating blood (Dobbelaere and Heussler, 1999). Subsequently, the merozoites released upon lysis of the infected leukocytes progress to infect host erythrocytes (RBCs) and then develop into piroplasms. Although enlarged cells containing structures suggestive of schizonts have been identified in the lymph nodes, spleen and liver of T. orientalis-infected cattle (Sato et al., 1993), the details of schizont development remain unclear in non-transforming Theileria (Sugimoto and Fujisaki, 2002). For T. annulata, further multiplication of the piroplasms (merogony) occurs in the RBCs, while it is limited in T. parva (Conrad et al., 1986). In non-transforming Theileria, merogony has been observed in RBCs (Kawamoto et al., 1990). Finally, when the ticks feed on an infected host, they acquire blood-stage Theileria parasites, including the gametes. The gametes undergo sexual reproduction in the midgut of the vector competent tick species, where genetic recombination occurs during meiosis (Katzer et al., 2006, Morzaria et al., 1993, Weir et al., 2007). Theileria parasites are trans-stadially transmitted by the tick vectors; therefore, the known transmission vectors are usually 2- or 3-host tick species (Bishop et al., 2004).

Although a number of studies have described the evolution of piroplasmids (Babesia and Theileria), their findings have often differed from each other, with no single conclusion forthcoming (Criado-Fornelio et al., 2003, Lack et al., 2012). Contrasting timescales have been estimated by different researchers for the divergence time of the piroplasma, based on different genes and methodologies (Criado-Fornelio et al., 2003, Gou et al., 2013, Lack et al., 2012). In addition, one of the major controversies related to piroplasmid evolution is whether these parasites evolved first in vertebrate hosts or in ticks. Scientists are divided on this, and have based their conclusions on various assumptions and arguments (Criado-Fornelio et al., 2003, Schnittger et al., 2012).

Protozoan parasites are thought to have evolved genetic diversity to survive the immunologically unfavorable environments of their hosts. Genetic diversity often results in antigenic variation in parasites, thereby enabling them to escape the immune responses of their hosts (Deitsch et al., 2009). Recombination during sexual reproduction is probably a major mechanism underlying the genetic diversity of Theileria species (Henson et al., 2012, Katzer et al., 2006, Morzaria et al., 1993, Weir et al., 2007). Bioinformatic analyses have revealed genetic recombination to be a possible mechanism generating genetic diversity in genes such as the polymorphic immunodominant molecule (PIM) of T. parva and the T. annulata surface protein (TaSP) (Geysen et al., 2004, Schnittger et al., 2002). In addition to genetic recombination, mutations in the epitopes of CD8+ cytotoxic T lymphocyte (CTL) antigens were found to facilitate immune evasion in T. parva (Connelley et al., 2011). While the evolutionary acquisition of genetic diversity is beneficial to the long-term survival of the parasites, it often complicates the establishment of control measures against the diseases caused by them. Therefore, a thorough knowledge of genetic diversity in Theileria parasites is essential if we are to gain better understanding of these harmful organisms. In this review, we summarize the findings of past studies on the evolution and genetic diversity of T. parva, T. annulata, and T. orientalis. We also discuss the possible relationships between genetic diversity, host specificity, and virulence.

Section snippets

Evolution of Theileria: an overview

Evolutionary studies are essential for understanding the biological behaviors of living things. Despite the economic significance of Theileria parasites, detailed studies have not been conducted to investigate their evolutionary processes. Therefore, in this review, we summarize the relevant findings of previous work and provide an outline of Theileria evolution.

Genetic diversity: a Theileria survival strategy with implications for its control

Genetic diversity is considered to be the raw material for the evolution of living things (Whitehead and Crawford, 2006). Genetic variation within populations of Theileria is known to be one of the survival strategies used by these pathogens. The sophisticated mechanisms of genetic and epigenetic diversity, like the cases of VESA1 and variable surface glycoprotein (VSG) gene families of B. bovis and Trypanosoma brucei, respectively (Al-Khedery and Allred, 2006, Hoeijmakers et al., 1980, Myler

Concluding remarks

Attempts to unravel the evolutionary history of the piroplasmids, an order that includes Theileria parasites, has created controversy among researchers. However, what most researchers agree on is that our current knowledge does not provide a complete evolutionary picture of these parasites. The roles played by amphibians and reptiles have never been examined in the evolutionary studies, although, according to a report by Schnittger et al. (2012), they could have been involved in the early

Acknowledgments

This work was supported by Grants from the Science and Technology Research Promotion Program for Agriculture, Forestry, Fisheries and Food Industry, from the Japan Society for Promotion of Science (JSPS) Grant-in-Aid for Scientific Research, and from the JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS). We are thankful to two anonymous reviewers for their constructive comments that greatly improved the manuscript.

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