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Science 15 December 2006:
Vol. 314. no. 5806, pp. 1780 - 1783
DOI: 10.1126/science.1133690

Reports

Polymorphic Secreted Kinases Are Key Virulence Factors in Toxoplasmosis

J. P. J. Saeij,1* J. P. Boyle,1* S. Coller,1 S. Taylor,2 L. D. Sibley,2 E. T. Brooke-Powell,3 J. W. Ajioka,3 J. C. Boothroyd1{dagger}

The majority of known Toxoplasma gondii isolates from Europe and North America belong to three clonal lines that differ dramatically in their virulence, depending on the host. To identify the responsible genes, we mapped virulence in F1 progeny derived from crosses between type II and type III strains, which we introduced into mice. Five virulence (VIR) loci were thus identified, and for two of these, genetic complementation showed that a predicted protein kinase (ROP18 and ROP16, respectively) is the key molecule. Both are hypervariable rhoptry proteins that are secreted into the host cell upon invasion. These results suggest that secreted kinases unique to the Apicomplexa are crucial in the host-pathogen interaction.

1 Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
2 Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
3 Department of Pathology, Cambridge University, Cambridge, CB2 1QP, UK.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: john.boothroyd{at}stanford.edu

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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S. Fauquenoy, W. Morelle, A. Hovasse, A. Bednarczyk, C. Slomianny, C. Schaeffer, A. Van Dorsselaer, and S. Tomavo (2008)
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Organellar dynamics during the cell cycle of Toxoplasma gondii.
M. Nishi, K. Hu, J. M. Murray, and D. S. Roos (2008)
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Phosphoinositide-3-Kinase-Dependent, MyD88-Independent Induction of CC-Type Chemokines Characterizes the Macrophage Response to Toxoplasma gondii Strains with High Virulence.
C. W. Lee, W. Sukhumavasi, and E. Y. Denkers (2007)
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Presentation of Toxoplasma gondii Antigens via the Endogenous Major Histocompatibility Complex Class I Pathway in Nonprofessional and Professional Antigen-Presenting Cells.
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Discovery of parasite virulence genes reveals a unique regulator of chromosome condensation 1 ortholog critical for efficient nuclear trafficking.
M. B. Frankel, D. G. Mordue, and L. J. Knoll (2007)
PNAS 104, 10181-10186
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Science. ISSN 0036-8075 (print), 1095-9203 (online)