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Eukaryotic Cell, April 2004, p. 495-505, Vol. 3, No. 2
1535-9778/04/$08.00+0     DOI: 10.1128/EC.3.2.495-505.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

A Theileria annulata DNA Binding Protein Localized to the Host Cell Nucleus Alters the Phenotype of a Bovine Macrophage Cell Line

Brian R. Shiels,1* Sue McKellar,1 Frank Katzer,1,{dagger} Kim Lyons,1,{ddagger} Jane Kinnaird,1 Chris Ward,2 Jonathan M. Wastling,2 and David Swan1

Department of Veterinary Parasitology, Institute of Comparative Medicine, University of Glasgow, Glasgow G61 1QH,1 Division of Infection and Immunity, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, United Kingdom2

Received 18 August 2003/ Accepted 25 November 2003

The apicomplexan parasite Theileria annulata is the only intracellular eukaryote that is known to induce the proliferation of mammalian cells. However, as the parasite undergoes stage differentiation, host cell proliferation is inhibited, and the leukocyte is eventually destroyed. We have isolated a parasite gene (SuAT1) encoding an AT hook DNA binding polypeptide that has a predicted signal peptide, PEST motifs, nuclear localization signals, and domains which indicate interaction with regulatory components of the higher eukaryotic cell cycle. The polypeptide is localized to the nuclei of macroschizont-infected cells and was detected at significant levels in cells that were undergoing parasite stage differentiation. Transfection of an uninfected transformed bovine macrophage cell line, BoMac, demonstrated that SuAT1 can modulate cellular morphology and alter the expression pattern of a cytoskeletal polypeptide in a manner similar to that found during the infection of leukocytes by the parasite. Our findings indicate that Theileria parasite molecules that are transported to the leukocyte nucleus have the potential to modulate the phenotype of infected cells.

* Corresponding author. Mailing address: Department of Veterinary Parasitology, Institute of Comparative Medicine, University of Glasgow, Glasgow G61 1QH, United Kingdom. Phone: 011 44 141 330 5756. Fax: 011 44 141 330 5603. E-mail: B.Shiels{at}vet.gla.ac.uk.

{dagger} Present address: Department of Tropical Animal Health, University of Edinburgh, Easter Bush, Roslin EH25 9RG, Scotland, United Kingdom.

{ddagger} Present address: Malaria Biology, Queensland Institute of Medical Research, Herston 4029, Queensland, Australia.

Eukaryotic Cell, April 2004, p. 495-505, Vol. 3, No. 2
1535-9778/04/$08.00+0     DOI: 10.1128/EC.3.2.495-505.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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