A bovine lymphosarcoma cell line infected with theileria annulata exhibits an irreversible reconfiguration of host cell gene expression

Kinnaird, J.H., Weir, W. , Durrani, Z., Pillai, S.S., Baird, M. and Shiels, B.R. (2013) A bovine lymphosarcoma cell line infected with theileria annulata exhibits an irreversible reconfiguration of host cell gene expression. PLoS ONE, 8(6), e66833. (doi:10.1371/journal.pone.0066833) (PMID:23840536) (PMCID:PMC3694138)

Kinnaird, J.H., Weir, W. , Durrani, Z., Pillai, S.S., Baird, M. and Shiels, B.R. (2013) A bovine lymphosarcoma cell line infected with theileria annulata exhibits an irreversible reconfiguration of host cell gene expression. PLoS ONE, 8(6), e66833. (doi:10.1371/journal.pone.0066833) (PMID:23840536) (PMCID:PMC3694138)

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Abstract

Theileria annulata, an intracellular parasite of bovine lymphoid cells, induces substantial phenotypic alterations to its host cell including continuous proliferation, cytoskeletal changes and resistance to apoptosis. While parasite induced modulation of host cell signal transduction pathways and NFκB activation are established, there remains considerable speculation on the complexities of the parasite directed control mechanisms that govern these radical changes to the host cell. Our objectives in this study were to provide a comprehensive analysis of the global changes to host cell gene expression with emphasis on those that result from direct intervention by the parasite. By using comparative microarray analysis of an uninfected bovine cell line and its Theileria infected counterpart, in conjunction with use of the specific parasitacidal agent, buparvaquone, we have identified a large number of host cell gene expression changes that result from parasite infection. Our results indicate that the viable parasite can irreversibly modify the transformed phenotype of a bovine cell line. Fifty percent of genes with altered expression failed to show a reversible response to parasite death, a possible contributing factor to initiation of host cell apoptosis. The genes that did show an early predicted response to loss of parasite viability highlighted a sub-group of genes that are likely to be under direct control by parasite infection. Network and pathway analysis demonstrated that this sub-group is significantly enriched for genes involved in regulation of chromatin modification and gene expression. The results provide evidence that the Theileria parasite has the regulatory capacity to generate widespread change to host cell gene expression in a complex and largely irreversible manner.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Weir, Dr William and Shiels, Professor Brian and Baird, Mrs Margaret and Kinnaird, Dr Jane
Authors: Kinnaird, J.H., Weir, W., Durrani, Z., Pillai, S.S., Baird, M., and Shiels, B.R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN:1932-6203
Copyright Holders:Copyright © 2013 The Authors
First Published:First published in PLoS ONE 8(6):e66833
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
465051Investigation of molecular mechanisms deployed by Theileria annulata as an activator and modulator of host cell transcription factors.Brian ShielsWellcome Trust (WELLCOME)083488/Z/07/ZIII - PARASITOLOGY