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A. S. Young - One of the best experts on this subject based on the ideXlab platform.

  • Theileria parva carrier state in naturally infected and artificially immunised cattle
    Tropical Animal Health and Production, 1995
    Co-Authors: D. P. Kariuki, A. S. Young, S. P. Morzaria, A. C. Lesan, S. K. Mining, P. Omwoyo, J. L. M. Wafula, D. H. Molyneux
    Abstract:

    Des tiques adultes de Rhipicephalus appendiculatus récoltées sur des zébus ( Bos indicus ) et des bovins importés ( Bos taurus ) présentant des taux élevés d'anticorps vis à vis d'antigènes de schizontes de Theileria parva , ont transmis une infection à Th. parva typique de theileriose à des bovins sensibles. Des nymphes de R. appendiculatus non infectées, appliquées sur des zébus naturellement guéris et placées ultérieurement sur des bovins importés maintenus à l'abri des tiques pendant 16 et 17 mois respectivement on transmis une theileriose mortelle aux bovins sensibles. Les bovins immunisés par la méthode infection et traitement se sont révélés porteurs de Th. parva par l'examen des glandes salivaires de tiques fixées sur eux et par la transmission par les tiques, et 3 et 7 mois après immunisation des lymphocytes infectés par Th. parva ont été mis en évidence in vitro à partir des lymphocytes du sang periphérique. Il s'agit de la première observation, in vitro , de l'existence de schizontes chez des animaux porteurs de theileriose à Th. parva . Ces études montrent que les bovins des régions où sévit la theileriose à l'état épidémique où endémique deviennent porteurs, maintenant ainsi la population de Th. parva . Les observations lors de cette étude concernant la lutte contre la theileriose par l'utilisation de bains détiqueurs, l'immunisation et le traitement sont discutées. Garrapatas adultas Rhipicephalus appendiculatus , recolectadas en el campo en ganado cebú (Bos indicus) y ganado exótico (Bos taurus) con niveles altos de anticuerpos contra antígeno de esquizontes de Theileria parva , transmitieron la infección con Th. parva , típica de Fiebre de la Costa Este, a ganado susceptible. Las ninfas no infectadas de R. appendiculatus , aplicadas a cebú recuperado de la infección y a ganado exótico mantenidos libres de garrapatas en el laboratorio durante 16 y 7 meses respectivamente, transmitieron theileriosis fatal a ganado susceptible. El ganado inmunizado por infección y tratamiento posterior fueron portadores de Theileria parva mediante examen de las glándulas salivares de garrapatas nuevamente aplicadas a dicho ganado y mediante transmisión vectorial. Se pudieron establecer in vitro linfocitos infectados por Theileria parva , provenientes de la sangre periférica 3 y 7 meses después de la inmunización. Esta ha sido la primera demonstración in vitro de la existencia de esquizontes en el estado de portador en infecciones con Theileria parva . Este estudio demuestra que el ganado en áreas endémicas y epidémicas, permanece como portador, manteniendo asi la población de Th. parva . Se discute la importancia de este hallazgo, para el control de la Fiebre de la Costa Este mediante inmersión, inmunización y tratamiento. Rhipicephalus appendiculatus adult ticks, collected in the field from zebu ( Bos indicus ) and exotic ( Bos tarus ) cattle with high antibody titres to Theileria parva schizont antigen, transmitted Theileria parva infection typical of East Coast fever to susceptible cattle. Uninfected R. appendiculatus nymphs applied to naturally recovered zebu and exotic cattle kept under tick-free conditions in the laboratory for 16 and 7 months respectively, transmitted fatal theileriosis to susceptible cattle. Cattle immunised by the infection and treatment method were shown to be carriers of Theileria parva by examination of the salivary glands of ticks applied to them and by tick transmission. Three and 7 months after immunisation, Theileria parva infected lymphocytes were established in vitro from peripheral blood lymphocytes. This was the first demonstration, in vitro , of the existence of schizonts in Theileria parva (East Coast fever) infection carrier status. These studies show that cattle from endemic and epidemic areas of East Coast fever (ECF) become carriers thereby maintaining the T. parva population. The relevance of the findings in this study to the control of ECF by dipping, immunisation and treatment is discussed.

  • Characterization of Theileria parva which infects waterbuck (Kobus defassa).
    Parasitology, 1994
    Co-Authors: D.a. Stagg, S. P. Morzaria, D. H. Molyneux, R P Bishop, M K Shaw, D Wesonga, G O Orinda, J G Grootenhuis, A. S. Young
    Abstract:

    Theileria-free waterbuck (Kobus defassa) born in captivity were successfully infected with Theileria parva sporozoites derived from ticks infected by feeding on African buffalo (Syncerus caffer). All waterbuck underwent mild infections with the development of sporadic schizont and piroplasm parasitosis when inoculated with sporozoite doses lethal to cattle. A carrier state of T. parva was demonstrated by feeding clean R. appendiculatus nymphs on two of these infected waterbuck. Tick batches from these waterbuck on 2 of 5 occasions transmitted lethal Theileria infections to cattle. In a separate experiment, waterbuck cells were infected and transformed in vitro by T. parva sporozoites derived from buffalo but not by cattle-derived T. parva (Muguga) sporozoites. Waterbuck cells infected in vitro with T. parva isolated from buffalo were inoculated into autologous waterbuck but no infections developed. Theileria parva isolates generated in this study from various sources were characterized using anti-T. parva schizont monoclonal antibodies (MAbs), and it was found that buffalo-derived and waterbuck-passaged isolates had different profiles. Species-specific synthetic oligonucleotide probes, restriction fragment length polymorphism (RFLP) analysis with cloned T. parva DNA probes, and DNA sequence analysis of the p67 sporozoite antigen gene confirmed that the waterbuck-passaged parasite was T. parva. The Tpr repetitive probe hybridization patterns from the waterbuck-passaged parasites were different from the other samples tested. The ribosomal genotype of the waterbuck-passaged T. parva was similar to that of cattle-derived T. parva Muguga. Analyses with both probes and MAbs suggested that a minor parasite population present within the T. parva 7014 buffalo-derived stock had been selected during waterbuck passage.(ABSTRACT TRUNCATED AT 250 WORDS)

  • Characterization of Theileria parva which infects waterbuck (Kobus defassa)
    Parasitology, 1994
    Co-Authors: D.a. Stagg, S. P. Morzaria, Richard P. Bishop, M K Shaw, D Wesonga, G O Orinda, J G Grootenhuis, David H. Molyneux, A. S. Young
    Abstract:

    Theileria-free waterbuck (Kobus defassa) born in captivity were successfully infected with Theileria parva sporozoites derived from ticks infected by feeding on African buffalo (Syncerus caffer). All waterbuck underwent mild infections with the development of sporadic schizont and piroplasm parasitosis when inoculated with sporozoite doses lethal to cattle. A carrier state of T. parva was demonstrated by feeding clean R. appendiculatus nymphs on two of these infected waterbuck. Tick batches from these waterbuck on 2 of 5 occasions transmitted lethal Theileria infections to cattle. In a separate experiment, waterbuck cells were infected and transformed in vitro by T. parva sporozoites derived from buffalo but not by cattle-derived T. parva (Muguga) sporozoites

  • The naming game. The changing fortunes of East Coast fever and Theileria parva
    Veterinary Record, 1993
    Co-Authors: Bd Perry, A. S. Young
    Abstract:

    Since first being recognised at the turn of the century, East Coast fever of cattle and its causal parasite Theileria parva have undergone numerous name changes as scientists have observed differences in the distribution, severity, characteristics and host associations of the disease within Africa. These changes have caused considerable confusion to scientists and affected the control of infections caused by T parva in the field. The justification for the decisions affecting the nomenclature of T parva and the diseases it causes are documented and reviewed, and their validity is considered in the light of current knowledge. Areas of research required to clarify the remaining confusion are identified.

  • preliminary analysis of the transmission dynamics of Theileria parva in eastern africa
    Parasitology, 1993
    Co-Authors: G F Medley, Brian D Perry, A. S. Young
    Abstract:

    Two mathematical models are developed that investigate the transmission dynamics of Theileria parva by the ixodid tick Rhipicephalus appendiculatus to cattle in endemically stable areas. A method of estimating the rate of infection to cattle of T. parva at the endemically stable state is given. Empirical estimates of ail the parameters in the model are available. The degree to which animals that have recovered from theileriosis (the ‘carrier’ state) are able to transmit the infection to tick nymphs or larvae is a crucial determinant of the dynamics of infection in a herd. Two control methods influencing the transmission of infection are considered – infection and treatment immunization and the reduction in tick feeding by acaricide application. The impact of each method on the transmission of infection is evaluated. Future developments and the data required to predict the dynamics of T. parva infections in cattle and ticks are discussed.

S. P. Morzaria - One of the best experts on this subject based on the ideXlab platform.

  • vaccines against Theileria parva
    Annals of the New York Academy of Sciences, 2006
    Co-Authors: S. P. Morzaria, Vishvanath Nene, Richard P. Bishop, Antony Musoke
    Abstract:

    : Bovine theileriosis caused by Theileria parva continues to be a major economic problem in many parts of Eastern, Southern, and Central Africa. Due to the unsustainable nature of the present control method-using toxic acaricides to kill ticks-alternative control methods are being sought. Live vaccines are being used in many countries in the region. These vaccines are based on the infective sporozoite stage of the parasite. Sporozoites are inoculated in cattle with simultaneous administration of a long-acting formulation of oxytetracycline. These vaccines are poorly adopted in the region, mainly because of problems associated with the use of live parasites. An experimental recombinant vaccine based on a sporozoite surface antigen (p67) has been developed. Immunization with this antigen induces neutralizing antibodies and, under laboratory conditions, this technique protects approximately 70% of the immunized cattle to a defined needle challenge. The efficacy of the vaccine is currently being evaluated under field challenge in Kenya. Since a vaccine based on a single antigen may not be sustainable under field conditions, a search for schizont antigens that induce protective cell-mediated immune responses continues. It is expected that the ultimate vaccine against theileriosis will incorporate a mixture of several antigens derived from both sporozoite and schizont stages, contributing to robust immunity.

  • Theileria parva carrier state in naturally infected and artificially immunised cattle
    Tropical Animal Health and Production, 1995
    Co-Authors: D. P. Kariuki, A. S. Young, S. P. Morzaria, A. C. Lesan, S. K. Mining, P. Omwoyo, J. L. M. Wafula, D. H. Molyneux
    Abstract:

    Des tiques adultes de Rhipicephalus appendiculatus récoltées sur des zébus ( Bos indicus ) et des bovins importés ( Bos taurus ) présentant des taux élevés d'anticorps vis à vis d'antigènes de schizontes de Theileria parva , ont transmis une infection à Th. parva typique de theileriose à des bovins sensibles. Des nymphes de R. appendiculatus non infectées, appliquées sur des zébus naturellement guéris et placées ultérieurement sur des bovins importés maintenus à l'abri des tiques pendant 16 et 17 mois respectivement on transmis une theileriose mortelle aux bovins sensibles. Les bovins immunisés par la méthode infection et traitement se sont révélés porteurs de Th. parva par l'examen des glandes salivaires de tiques fixées sur eux et par la transmission par les tiques, et 3 et 7 mois après immunisation des lymphocytes infectés par Th. parva ont été mis en évidence in vitro à partir des lymphocytes du sang periphérique. Il s'agit de la première observation, in vitro , de l'existence de schizontes chez des animaux porteurs de theileriose à Th. parva . Ces études montrent que les bovins des régions où sévit la theileriose à l'état épidémique où endémique deviennent porteurs, maintenant ainsi la population de Th. parva . Les observations lors de cette étude concernant la lutte contre la theileriose par l'utilisation de bains détiqueurs, l'immunisation et le traitement sont discutées. Garrapatas adultas Rhipicephalus appendiculatus , recolectadas en el campo en ganado cebú (Bos indicus) y ganado exótico (Bos taurus) con niveles altos de anticuerpos contra antígeno de esquizontes de Theileria parva , transmitieron la infección con Th. parva , típica de Fiebre de la Costa Este, a ganado susceptible. Las ninfas no infectadas de R. appendiculatus , aplicadas a cebú recuperado de la infección y a ganado exótico mantenidos libres de garrapatas en el laboratorio durante 16 y 7 meses respectivamente, transmitieron theileriosis fatal a ganado susceptible. El ganado inmunizado por infección y tratamiento posterior fueron portadores de Theileria parva mediante examen de las glándulas salivares de garrapatas nuevamente aplicadas a dicho ganado y mediante transmisión vectorial. Se pudieron establecer in vitro linfocitos infectados por Theileria parva , provenientes de la sangre periférica 3 y 7 meses después de la inmunización. Esta ha sido la primera demonstración in vitro de la existencia de esquizontes en el estado de portador en infecciones con Theileria parva . Este estudio demuestra que el ganado en áreas endémicas y epidémicas, permanece como portador, manteniendo asi la población de Th. parva . Se discute la importancia de este hallazgo, para el control de la Fiebre de la Costa Este mediante inmersión, inmunización y tratamiento. Rhipicephalus appendiculatus adult ticks, collected in the field from zebu ( Bos indicus ) and exotic ( Bos tarus ) cattle with high antibody titres to Theileria parva schizont antigen, transmitted Theileria parva infection typical of East Coast fever to susceptible cattle. Uninfected R. appendiculatus nymphs applied to naturally recovered zebu and exotic cattle kept under tick-free conditions in the laboratory for 16 and 7 months respectively, transmitted fatal theileriosis to susceptible cattle. Cattle immunised by the infection and treatment method were shown to be carriers of Theileria parva by examination of the salivary glands of ticks applied to them and by tick transmission. Three and 7 months after immunisation, Theileria parva infected lymphocytes were established in vitro from peripheral blood lymphocytes. This was the first demonstration, in vitro , of the existence of schizonts in Theileria parva (East Coast fever) infection carrier status. These studies show that cattle from endemic and epidemic areas of East Coast fever (ECF) become carriers thereby maintaining the T. parva population. The relevance of the findings in this study to the control of ECF by dipping, immunisation and treatment is discussed.

  • Characterization of Theileria parva which infects waterbuck (Kobus defassa).
    Parasitology, 1994
    Co-Authors: D.a. Stagg, S. P. Morzaria, D. H. Molyneux, R P Bishop, M K Shaw, D Wesonga, G O Orinda, J G Grootenhuis, A. S. Young
    Abstract:

    Theileria-free waterbuck (Kobus defassa) born in captivity were successfully infected with Theileria parva sporozoites derived from ticks infected by feeding on African buffalo (Syncerus caffer). All waterbuck underwent mild infections with the development of sporadic schizont and piroplasm parasitosis when inoculated with sporozoite doses lethal to cattle. A carrier state of T. parva was demonstrated by feeding clean R. appendiculatus nymphs on two of these infected waterbuck. Tick batches from these waterbuck on 2 of 5 occasions transmitted lethal Theileria infections to cattle. In a separate experiment, waterbuck cells were infected and transformed in vitro by T. parva sporozoites derived from buffalo but not by cattle-derived T. parva (Muguga) sporozoites. Waterbuck cells infected in vitro with T. parva isolated from buffalo were inoculated into autologous waterbuck but no infections developed. Theileria parva isolates generated in this study from various sources were characterized using anti-T. parva schizont monoclonal antibodies (MAbs), and it was found that buffalo-derived and waterbuck-passaged isolates had different profiles. Species-specific synthetic oligonucleotide probes, restriction fragment length polymorphism (RFLP) analysis with cloned T. parva DNA probes, and DNA sequence analysis of the p67 sporozoite antigen gene confirmed that the waterbuck-passaged parasite was T. parva. The Tpr repetitive probe hybridization patterns from the waterbuck-passaged parasites were different from the other samples tested. The ribosomal genotype of the waterbuck-passaged T. parva was similar to that of cattle-derived T. parva Muguga. Analyses with both probes and MAbs suggested that a minor parasite population present within the T. parva 7014 buffalo-derived stock had been selected during waterbuck passage.(ABSTRACT TRUNCATED AT 250 WORDS)

  • Characterization of Theileria parva which infects waterbuck (Kobus defassa)
    Parasitology, 1994
    Co-Authors: D.a. Stagg, S. P. Morzaria, Richard P. Bishop, M K Shaw, D Wesonga, G O Orinda, J G Grootenhuis, David H. Molyneux, A. S. Young
    Abstract:

    Theileria-free waterbuck (Kobus defassa) born in captivity were successfully infected with Theileria parva sporozoites derived from ticks infected by feeding on African buffalo (Syncerus caffer). All waterbuck underwent mild infections with the development of sporadic schizont and piroplasm parasitosis when inoculated with sporozoite doses lethal to cattle. A carrier state of T. parva was demonstrated by feeding clean R. appendiculatus nymphs on two of these infected waterbuck. Tick batches from these waterbuck on 2 of 5 occasions transmitted lethal Theileria infections to cattle. In a separate experiment, waterbuck cells were infected and transformed in vitro by T. parva sporozoites derived from buffalo but not by cattle-derived T. parva (Muguga) sporozoites

  • Genome analysis of Theileria parva
    Parasitology Today, 1993
    Co-Authors: S. P. Morzaria, J.r. Young
    Abstract:

    Abstract Recent technological developments in the field of genome analyses have advanced our knowledge of the structures of prokaryotic and eukoryotic genomes. Examples of these range from small bacterial genomes, such as Escherichia coli , to the more complex genomes of Caenorhabditis elegans, Drosophila , humans and mouse. Here, Subhash Morzona and John Young review developments in mapping the genome of on economically important protozoan parasite o f cattle, Theileria parva . This map provides a framework for more detailed analysis of the genome structure o f this organism. The methodologies developed in constructing the map also have application to the mapping of other protozoan genomes.

Richard P. Bishop - One of the best experts on this subject based on the ideXlab platform.

  • Genomics of Theileria parva
    Theileria, 2020
    Co-Authors: Vishvanath Nene, Richard P. Bishop, John Quackenbush, Mihaela Pertea, Steven L. Salzberg, Evans L. N. Taracha, Subhash Morzaria, Claire M. Fraser, Malcolm J. Gardner
    Abstract:

    A project to determine the DNA sequence of the genome of Theileria parva, which consists of four chromosomes and two extra-chromosomal DNA molecules, is nearing completion. The random phase of genome sequence data generation has been finished and the process of gap closure is in progress. Repeat sequence DNA is more frequent than expected and this has complicated the assembly of sequence data while a paucity of characterized gene sequences has delayed the development of a Hidden Markov gene-prediction program. Sequence walks from unique regions and cDNA sequence data are primarily being used to address these issues, respectively. The identification of genes and assignment of potential gene function will provide an important framework for future research on T. parva. Annotation of the genome sequence is eagerly awaited, as it will allow the application of functional genomics to unravel the biology of this organism and facilitate vaccine development against East Coast fever. Comparative genome analyses with other apicomplexan organisms and in particular with other Theileria species will add value to the interpretation of T. parva genome sequence data and vice versa.

  • TparvaDB: a database to support Theileria parva vaccine development
    Database, 2011
    Co-Authors: Paul Visendi, Richard P. Bishop, Wanjiku Ng'ang'a, Wallace D. Bulimo, James Ochanda, Etienne P. De Villiers
    Abstract:

    We describe the development of TparvaDB, a comprehensive resource to facilitate research towards development of an East Coast fever vaccine, by providing an integrated user-friendly database of all genome and related data currently available for Theileria parva. TparvaDB is based on the Generic Model Organism Database (GMOD) platform. It contains a complete reference genome sequence, Expressed Sequence Tags (ESTs), Massively Parallel Signature Sequencing (MPSS) expression tag data and related information from both public and private repositories. The Artemis annotation workbench provides online annotation functionality. TparvaDB represents a resource that will underpin and promote ongoing East Coast fever vaccine development and biological research. Database URL: http://tparvadb.ilri.cgiar.org

  • Theileria parva candidate vaccine antigens recognized by immune bovine cytotoxic t lymphocytes
    Proceedings of the National Academy of Sciences of the United States of America, 2006
    Co-Authors: Simon P Graham, Nyerhovwo J. Tonukari, Etienne P. De Villiers, Yoshikazu Honda, Trushar Shah, Roger Pelle, Duncan Mwangi, Mat Yamage, Jane E Glew, Richard P. Bishop
    Abstract:

    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 naive 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.

  • vaccines against Theileria parva
    Annals of the New York Academy of Sciences, 2006
    Co-Authors: S. P. Morzaria, Vishvanath Nene, Richard P. Bishop, Antony Musoke
    Abstract:

    : Bovine theileriosis caused by Theileria parva continues to be a major economic problem in many parts of Eastern, Southern, and Central Africa. Due to the unsustainable nature of the present control method-using toxic acaricides to kill ticks-alternative control methods are being sought. Live vaccines are being used in many countries in the region. These vaccines are based on the infective sporozoite stage of the parasite. Sporozoites are inoculated in cattle with simultaneous administration of a long-acting formulation of oxytetracycline. These vaccines are poorly adopted in the region, mainly because of problems associated with the use of live parasites. An experimental recombinant vaccine based on a sporozoite surface antigen (p67) has been developed. Immunization with this antigen induces neutralizing antibodies and, under laboratory conditions, this technique protects approximately 70% of the immunized cattle to a defined needle challenge. The efficacy of the vaccine is currently being evaluated under field challenge in Kenya. Since a vaccine based on a single antigen may not be sustainable under field conditions, a search for schizont antigens that induce protective cell-mediated immune responses continues. It is expected that the ultimate vaccine against theileriosis will incorporate a mixture of several antigens derived from both sporozoite and schizont stages, contributing to robust immunity.

  • genome sequence of Theileria parva a bovine pathogen that transforms lymphocytes
    Science, 2005
    Co-Authors: Malcolm J. Gardner, Richard P. Bishop, Etienne P. De Villiers, Trushar Shah, Jane M Carlton, Neil Hall, Ian T Paulsen, Arnab Pain, Matthew Berriman, Robert John Macleod Wilson
    Abstract:

    We report the genome sequence of Theileria parva, an apicomplexan pathogen causing economic losses to smallholder farmers in Africa. The parasite chromosomes exhibit limited conservation of gene synteny with Plasmodium falciparum, and its plastid-like genome represents the first example where all apicoplast genes are encoded on one DNA strand. We tentatively identify proteins that facilitate parasite segregation during host cell cytokinesis and contribute to persistent infection of transformed host cells. Several biosynthetic pathways are incomplete or absent, suggesting substantial metabolic dependence on the host cell. One protein family that may generate parasite antigenic diversity is not telomere-associated.

Dirk A. E. Dobbelaere - One of the best experts on this subject based on the ideXlab platform.

  • Identification of a surface antigen on Theileria parva sporozoites by
    2020
    Co-Authors: Dirk A. E. Dobbelaere, Stuart Z. Shapiro, Paul Webster
    Abstract:

    A mouse monoclonal antibody (mAbD1) that neutralizes sporozoites of different stocks of the protozoan parasite Theileria parva has been used to localize and identify a sporozoite antigen. Protein A-colloidal gold was used to local- ize bound mAbDl in immunoelectron microscopic studies. mAbDl bound to sporozoite antigen, which was evenly spread over the surface of all sporozoites. Immune complexes were obtained by incubation of sporozoite suspensions with mAbDl followed by Zwittergent 3-14 extraction and precipitation with protein A-Sepharose. One- and two-dimensional NaDodSO4/ polyacrylamide gel electrophoretic analyses were performed on these complexes, and a major protein antigen with a molec- ular size of 68 kDa was identified. Other related components of 52 kDa, 47 kDa, and 28 kDa were also detected. Since anti- body to this antigen(s) neutralizes T. parva sporozoites from different stocks, the results could be of relevance to the devel- opment of a broad spectrum vaccine against the cattle disease East Coast fever, which is caused by T. parva.

  • a Theileria parva isolate of low virulence infects a subpopulation of lymphocytes
    Infection and Immunity, 2012
    Co-Authors: Dirk Geysen, Elias Awino, Dirk A. E. Dobbelaere, Heshborne S Tindih, Bruno Goddeeris, Jan Naessens
    Abstract:

    Theileria parva is a tick-transmitted protozoan parasite that infects and transforms bovine lymphocytes. We have previously shown that Theileria parva Chitongo is an isolate with a lower virulence than that of T. parva Muguga. Lower virulence appeared to be correlated with a delayed onset of the logarithmic growth phase of T. parva Chitongo-transformed peripheral blood mononuclear cells after in vitro infection. In the current study, infection experiments with WC1+ γδ T cells revealed that only T. parva Muguga could infect these cells and that no transformed cells could be obtained with T. parva Chitongo sporozoites. Subsequent analysis of the susceptibility of different cell lines and purified populations of lymphocytes to infection and transformation by both isolates showed that T. parva Muguga sporozoites could attach to and infect CD4+, CD8+, and WC1+ T lymphocytes, but T. parva Chitongo sporozoites were observed to bind only to the CD8+ T cell population. Flow cytometry analysis of established, transformed clones confirmed this bias in target cells. T. parva Muguga-transformed clones consisted of different cell surface phenotypes, suggesting that they were derived from either host CD4+, CD8+, or WC1+ T cells. In contrast, all in vitro and in vivo T. parva Chitongo-transformed clones expressed CD8 but not CD4 or WC1, suggesting that the T. parva Chitongo-transformed target cells were exclusively infected CD8+ lymphocytes. Thus, a role of cell tropism in virulence is likely. Since the adhesion molecule p67 is 100% identical between the two strains, a second, high-affinity adhesin that determines target cell specificity appears to exist.

  • transformation of leukocytes by Theileria parva and t annulata
    Annual Review of Microbiology, 1999
    Co-Authors: Dirk A. E. Dobbelaere, Volker Heussler
    Abstract:

    ▪ Abstract Theileria parva and T. annulata provide intriguing models for the study of parasite-host interactions. Both parasites possess the unique property of being able to transform the cells they infect; T. parva transforms T and B cells, whereas T. annulata affects B cells and monocytes/macrophages. Parasitized cells do not require antigenic stimulation or exogenous growth factors and acquire the ability to proliferate continuously. In vivo, parasitized cells undergo clonal expansion and infiltrate both lymphoid and non-lymphoid tissues of the infected host. Theileria-induced transformation is entirely reversible and is accompanied by the expression of a wide range of different lymphokines and cytokines, some of which may contribute to proliferation or may enhance spread and survival of the parasitized cell in the host. The presence of the parasite in the host-cell cytoplasm modulates the state of activation of a number of signal transduction pathways. This, in turn, leads to the activation of transcr...

  • The molecular basis of transformation of lymphocytes by Theileria parva infection.
    Seminars in Cell Biology, 1993
    Co-Authors: Richard O. Williams, Dirk A. E. Dobbelaere
    Abstract:

    Abstract The protozoan intracellular parasites, Theileria parva and Theileria annulata, infect cattle and cause severe and fatal leukocytic proliferative diseases. The proliferation is dependent on the presence of the parasites in the host cell cytoplasm. T. parva-infected cells proliferate permanently in cell culture and exhibit many features characteristic of tumor cells. The proliferation is reversible by treatment with parasite-specific drugs. Constitutive expression of interleukin-2, its receptor and their transcription factor, NF-κB, are dependent on the parasite and suggest autocrine growth. Cell-cell contact possibly via T cell adhesion molecules has been shown to stimulate proliferation.

Vishvanath Nene - One of the best experts on this subject based on the ideXlab platform.

  • Genomics of Theileria parva
    Theileria, 2020
    Co-Authors: Vishvanath Nene, Richard P. Bishop, John Quackenbush, Mihaela Pertea, Steven L. Salzberg, Evans L. N. Taracha, Subhash Morzaria, Claire M. Fraser, Malcolm J. Gardner
    Abstract:

    A project to determine the DNA sequence of the genome of Theileria parva, which consists of four chromosomes and two extra-chromosomal DNA molecules, is nearing completion. The random phase of genome sequence data generation has been finished and the process of gap closure is in progress. Repeat sequence DNA is more frequent than expected and this has complicated the assembly of sequence data while a paucity of characterized gene sequences has delayed the development of a Hidden Markov gene-prediction program. Sequence walks from unique regions and cDNA sequence data are primarily being used to address these issues, respectively. The identification of genes and assignment of potential gene function will provide an important framework for future research on T. parva. Annotation of the genome sequence is eagerly awaited, as it will allow the application of functional genomics to unravel the biology of this organism and facilitate vaccine development against East Coast fever. Comparative genome analyses with other apicomplexan organisms and in particular with other Theileria species will add value to the interpretation of T. parva genome sequence data and vice versa.

  • A recombinant sporozoite surface antigen of Theileria parva induces
    2020
    Co-Authors: Antony Musoke, Subhash Morzaria, Catherine Nkonge, Vishvanath Nene
    Abstract:

    At present immunization against Theileria parva is by infection with live sporozoites and simultaneous treatment with a long-acting oxytetracycline. This method has major limitations in that live organisms are used and the immunity engendered is parasite stock specific. In an attempt to develop an alternative immunization procedure, the gene encoding p67, a major surface antigen of sporozoites, has been expressed by using the plasmid expression vector pMG1. The gene, which has been characterized previously, encodes 709 amino acid residues, contains a single intron of 29 base pairs, and is only transcribed during sporogony. The recombinant p67 sequences were fused to the first 85 amino acid residues derived from a nonstructural gene (NS1) of influenza virus A. Immunization with a partially purified recombinant antigen emulsified in 3% saponin induced sporozoite neutralizing antibodies in cattle and provided protection in six of nine animals on homologous challenge with T. parva sporozoites. This recombinant antigen is therefore a candidate for devel- opment of a vaccine against T. parva.

  • characterization of the Theileria parva sporozoite proteome
    International Journal for Parasitology, 2017
    Co-Authors: Kyle Tretina, Roger Pelle, Joana C Silva, James Nyagwange, Edwin Tijhaar, Nicola Ternette, Fredrick Mobegi, Vishvanath Nene
    Abstract:

    Abstract East Coast fever is a lymphoproliferative disease caused by the tick-borne protozoan parasite Theileria parva. The sporozoite stage of this parasite, harboured and released from the salivary glands of the tick Rhipicephalus appendiculatus during feeding, invades and establishes infection in bovine lymphocytes. Blocking this initial stage of invasion presents a promising vaccine strategy for control of East Coast fever and can in part be achieved by targeting the major sporozoite surface protein p67. To support research on the biology of T. parva and the identification of additional candidate vaccine antigens, we report on the sporozoite proteome as defined by LC–MS/MS analysis. In total, 4780 proteins were identified in an enriched preparation of sporozoites. Of these, 2007 were identified as T. parva proteins, representing close to 50% of the total predicted parasite proteome. The remaining 2773 proteins were derived from the tick vector. The identified sporozoite proteins include a set of known T. parva antigens targeted by antibodies and cytotoxic T cells from cattle that are immune to East Coast fever. We also identified proteins predicted to be orthologs of Plasmodium falciparum sporozoite surface molecules and invasion organelle proteins, and proteins that may contribute to the phenomenon of bovine lymphocyte transformation. Overall, these data establish a protein expression profile of T. parva sporozoites as an important starting point for further study of a parasitic species which has considerable agricultural impact.

  • vaccines against Theileria parva
    Annals of the New York Academy of Sciences, 2006
    Co-Authors: S. P. Morzaria, Vishvanath Nene, Richard P. Bishop, Antony Musoke
    Abstract:

    : Bovine theileriosis caused by Theileria parva continues to be a major economic problem in many parts of Eastern, Southern, and Central Africa. Due to the unsustainable nature of the present control method-using toxic acaricides to kill ticks-alternative control methods are being sought. Live vaccines are being used in many countries in the region. These vaccines are based on the infective sporozoite stage of the parasite. Sporozoites are inoculated in cattle with simultaneous administration of a long-acting formulation of oxytetracycline. These vaccines are poorly adopted in the region, mainly because of problems associated with the use of live parasites. An experimental recombinant vaccine based on a sporozoite surface antigen (p67) has been developed. Immunization with this antigen induces neutralizing antibodies and, under laboratory conditions, this technique protects approximately 70% of the immunized cattle to a defined needle challenge. The efficacy of the vaccine is currently being evaluated under field challenge in Kenya. Since a vaccine based on a single antigen may not be sustainable under field conditions, a search for schizont antigens that induce protective cell-mediated immune responses continues. It is expected that the ultimate vaccine against theileriosis will incorporate a mixture of several antigens derived from both sporozoite and schizont stages, contributing to robust immunity.

  • Organisation and informational content of the Theileria parva genome.
    Molecular and Biochemical Parasitology, 1998
    Co-Authors: Vishvanath Nene, Subhash Morzaria, Richard P. Bishop
    Abstract:

    Abstract When compared with other Apicomplexan organisms, Theileria parva has an exceptionally small, 10–12 Mbp, genome. There are only 4 chromosomes, each in the Mbp range, and a complete physical map, based on SfiI linking data, is available for each one. A number of genes and cDNAs have been mapped to specific SfiI fragments. Telomeres consist of the simple repeat sequence typical of chromosomal ends but sub-telomeric homologies do not extend beyond 5 kbp. The only dispersed repetitive sequences identified to date are minisatellites, but these are found on a subset of SfiI fragments. There are clusters of distinct multicopy sequences which contain ORFs. However, the majority of parasite protein coding genes are present in a single copy. They have a compact structure, exhibit a bias in codon usage and non-translated regions are small. Introns, if present, are unusually short. Overall, the genome contains remarkably little repetitive, non-coding DNA. The parasite mitochondrial DNA is linear in structure, has a limited protein coding capacity and fragmented rRNA genes and its telomeres contain inverted repeat sequences.