Genome Sequence of
            <i>Theileria parva</i>
            , a Bovine Pathogen That Transforms Lymphocytes

Gardner, Malcolm J.; Bishop, Richard P.; Shah, Trushar; Villiers, Etienne P. de; Carlton, Jane M.; Hall, Neil; Ren, Qinghu; Paulsen, Ian T.; Pain, Arnab; Berriman, Matthew; Wilson, Robert; Sato, Shigeharu; Ralph, Stuart A.; Mann, David J.; Xiong, Zikai; Shallom, Shamira; Weidman, Janice M.; Jiang, Lingxia; Lynn, Jeffery; Weaver, Bruce; Shoaibi, Azadeh; Domingo, Alexander R.; Wasawo, Delia; Crabtree, Jonathan; Wortman, Jennifer; Haas, Brian J.; Angiuoli, Samuel V.; Creasy, Todd; Lu, Charles; Suh, Bernard; Silva, Joana C.; Utterback, Teresa; Feldblyum, Tamara; Pertea, Mihaela; Allen, Jonathan; Nierman, William C.; Taracha, Evans; Salzberg, Steven L.; White, Owen; Fitzhugh, Henry A.; Morzaria, S.P.; Venter, J. Craig; Fraser, Claire M.; Nene, Vishvanath

doi:10.1126/science.1110439

Cited by 294 publications

(250 citation statements)

References 29 publications

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“…A subset of these sequences was associated with a range of metabolic functions. Of these, we noted that restricted to the Theileria were eight choline kinase proteins: an enzyme involved in lipid metabolism and implicated in host cell transformation (Gardner et al 2005). A phylogenetic reconstruction of the parasite proteins with other choline kinases from UniProt placed many of the Figure 2.…”

Section: Taxonomic Distribution Of Apicomplexan Proteinsmentioning

confidence: 99%

“…The complete genomes of six apicomplexans are currently available ( Fig. 2; Carlton et al 2002;Gardner et al 2002Gardner et al , 2005Abrahamsen et al 2004;Xu et al 2004;Pain et al 2005). Furthermore, large expressed sequence tag (EST) collections have been generated for an additional nine species (Ajioka et al 1998;Howe 2001;Li et al 2003a;Cui et al 2005), which can be used to construct so-called ''partial genomes '' (Peregrin-Alvarez and Parkinson 2007;Wasmuth et al 2008).…”

mentioning

confidence: 99%

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The origins of apicomplexan sequence innovation

Wasmuth¹,

Daub²,

Peregrín-Alvarez³

et al. 2009

Genome Res.

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The Apicomplexa are a group of phylogenetically related parasitic protists that include Plasmodium, Cryptosporidium, and Toxoplasma. Together they are a major global burden on human health and economics. To meet this challenge, several international consortia have generated vast amounts of sequence data for many of these parasites. Here, we exploit these data to perform a systematic analysis of protein family and domain incidence across the phylum. A total of 87,736 protein sequences were collected from 15 apicomplexan species. These were compared with three protein databases, including the partial genome database, PartiGeneDB, which increases the breadth of taxonomic coverage. From these searches we constructed taxonomic profiles that reveal the extent of apicomplexan sequence diversity. Sequences without a significant match outside the phylum were denoted as apicomplexan specialized. These were collated into 9134 discrete protein families and placed in the context of the apicomplexan phylogeny, identifying the putative origin of each family. Most apicomplexan families were associated with an individual genus or species. Interestingly, many genera-specific innovations were associated with specialized host cell invasion and/or parasite survival processes. Contrastingly, those families reflecting more ancestral relationships were enriched in generalized housekeeping functions such as translation and transcription, which have diverged within the apicomplexan lineage. Protein domain searches revealed 192 domains not previously reported in apicomplexans together with a number of novel domain combinations. We highlight domains that may be important to parasite survival.

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Section: Taxonomic Distribution Of Apicomplexan Proteinsmentioning

confidence: 99%

mentioning

confidence: 99%

The origins of apicomplexan sequence innovation

Wasmuth¹,

Daub²,

Peregrín-Alvarez³

et al. 2009

Genome Res.

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“…Proteomic evidence suggests the expression of a third MACPF-domain protein (PPLP4) in ookinetes but it has not been functionally characterized to date. 8 A second instance of an ApiPLP required for traversal of a cellular barrier was revealed by the disruption of PPLP1/SPECT2, which is expressed in Plasmodium salivary gland sporozoites. 12 Following the bite of an infectious mosquito, sporozoites enter disrupt the newly forming PVM and leads to productive invasion.…”

Section: Functionmentioning

confidence: 99%

“…Furthermore, the availability of supporting data sets such as stage specific expressing of varies greatly from the microarray, proteomics and expansive EST data available for Plasmodium 6 to only a limited number of Babesia ESTs sequenced. 7 While genomic sequences and gene predictions are available for six species of Plasmodium (falciparum, vivax, chabaudi, knowlesi, yoelii and berghei) and two species of Theileria (annulata and parva), 8,9 intra-genus orthology is very high both with respect to sequence identity and the number of MACPF-domain proteins predicted for each species within these genera. For this reason the ApiPLPs of Plasmodium and Theileria will be discussed on the genus level using the P. falciparum and T. annulata gene predictions as representatives.…”

Section: Introductionmentioning

confidence: 99%

Apicomplexan perforin-like proteins

Kafsack

Carruthers

2010

Communicative & Integrative Biology

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“…We adopted two approaches to antigen identification, both dependent on screening of transiently transfected antigenpresenting cells with fully characterized CTL (8,9) from live vaccine-immunized cattle of diverse bovine leukocyte antigen (BoLA) MHC class I genotypes. First, in a targeted gene approach, we immunoscreened genes that were predicted by using preliminary sequence data from one of the four T. parva chromosomes (10) to contain a secretion signal. The approach was based on the observation that the schizont lies free in the host cell cytoplasm (11) whereby signal peptide-containing parasite proteins would directly access the host cell MHC class I antigen processing and presentation pathway.…”

mentioning

confidence: 99%

Theileria parvacandidate vaccine antigens recognized by immune bovine cytotoxic T lymphocytes

Graham

Pellé

Honda

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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East Coast fever, caused by the tick-borne intracellular apicomplexan parasite Theileria parva, is a highly fatal lymphoproliferative disease of cattle. The pathogenic schizont-induced lymphocyte transformation is a unique cancer-like condition that is reversible with parasite removal. Schizont-infected cell-directed CD8 ؉ cytotoxic T lymphocytes (CTL) constitute the dominant protective bovine immune response after a single exposure to infection. However, the schizont antigens targeted by T. parva-specific CTL are undefined. Here we show the identification of five candidate vaccine antigens that are the targets of MHC class I-restricted CD8 ؉ CTL from immune cattle. CD8 ؉ T cell responses to these antigens were boosted in T. parva-immune cattle resolving a challenge infection and, when used to immunize naïve cattle, induced CTL responses that significantly correlated with survival from a lethal parasite challenge. These data provide a basis for developing a CTL-targeted anti-East Coast fever subunit vaccine. In addition, orthologs of these antigens may be vaccine targets for other apicomplexan parasites.cattle ͉ East Coast fever ͉ immunoscreening ͉ protozoan parasite ͉ vaccination A single inoculation with a potentially lethal dose of Theileria parva sporozoites and simultaneous treatment with a longacting oxytetracycline induces solid immunity to homologous and, in certain instances, heterologous parasite challenge (1, 2). This methodology has been adopted as a live vaccine for the control of East Coast fever (ECF) (3). The long-lasting immunity to ECF contrasts with the partial immunity to malaria that develops after only several years of exposure to T. parva-related Plasmodium spp. (4). Manufacture and delivery of the live ECF vaccine is difficult to sustain, but it has enabled elucidation of the dominant protective immune response against the disease. Kinetic and adoptive cell transfer studies (5, 6) have demonstrated that protection of cattle is mediated by MHC class I-restricted CD8 ϩ cytotoxic T lymphocytes (CTL) that destroy schizontinfected lymphocytes, the pathogenic life-cycle stage of T. parva. In addition, there is a strong correlation between the specificity of the CTL response and cross-immunity profiles of distinct parasite strains (2). The identification of schizont antigens targeted by CTL from T. parva-immune cattle has been elusive but should pave the way for the development of a subunit vaccine against ECF and provide a long-term solution to a socioeconomically important constraint to livestock agriculture in Africa (7). We adopted two approaches to antigen identification, both dependent on screening of transiently transfected antigenpresenting cells with fully characterized CTL (8, 9) from live vaccine-immunized cattle of diverse bovine leukocyte antigen (BoLA) MHC class I genotypes. First, in a targeted gene approach, we immunoscreened genes that were predicted by using preliminary sequence data from one of the four T. parva chromosomes (10) to contain a secretion signal. The approach was ...

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Genome Sequence of Theileria parva , a Bovine Pathogen That Transforms Lymphocytes

Cited by 294 publications

References 29 publications

The origins of apicomplexan sequence innovation

The origins of apicomplexan sequence innovation

Apicomplexan perforin-like proteins

Theileria parvacandidate vaccine antigens recognized by immune bovine cytotoxic T lymphocytes

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