A Theileria annulata DNA binding protein localized to the host cell nucleus alters the phenotype of a bovine macrophage cell line.
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.
Shiels
Brian R
BR
Department of Veterinary Parasitology, Institute of Comparative Medicine, University of Glasgow, Glasgow G61 1QH, United Kingdom. B.Shiels@vet.gla.ac.uk
McKellar
Sue
S
Katzer
Frank
F
Lyons
Kim
K
Kinnaird
Jane
J
Ward
Chris
C
Wastling
Jonathan M
JM
Swan
David
D
D024761:AT-Hook Motifs; D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D002417:Cattle / Q000469:parasitology*; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D002934:Cinnamates / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D006921:Hygromycin B / Q000031:analogs & derivatives* / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism / Q000469:parasitology* / Q000648:ultrastructure; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D010641:Phenotype; D011485:Protein Binding; D015800:Protozoan Proteins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D016796:Theileria annulata / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D014162:Transfection
D000913:Antibodies, Protozoan; D002934:Cinnamates; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D015800:Protozoan Proteins; D006921:Hygromycin B; C026273:hygromycin A