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Journal of Virology, June 2006, p. 5644-5650, Vol. 80, No. 11
0022-538X/06/$08.00+0     doi:10.1128/JVI.02400-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Measles Virus V Protein Inhibits p53 Family Member p73

Cristian D. Cruz,1,{dagger} Heidi Palosaari,1,{dagger} Jean-Patrick Parisien,1,{dagger} Patricia Devaux,2 Roberto Cattaneo,2 Toru Ouchi,3 and Curt M. Horvath1*

Department of Medicine and Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois, and Department of Medicine, Evanston Northwestern Healthcare, Evanston, Illinois 60208,1 Molecular Medicine Program, Mayo Clinic College of Medicine, Rochester, Minnesota 55905,2 Department of Oncological Sciences, Mount Sinai School of Medicine, New York, New York 100293

Received 15 November 2005/ Accepted 11 March 2006

Paramyxovirus V proteins function as host interference factors that inactivate antiviral responses, including interferon. Characterization of cellular proteins that copurify with ectopically expressed measles virus V protein has revealed interactions with DNA binding domains of p53 family proteins, p53 and p73. Specific transcriptional assays reveal that expression of measles virus V cDNA inhibits p73, but not p53. Expression of measles virus V cDNA can delay cell death induced by genotoxic stress and also can decrease the abundance of the proapoptotic factor PUMA, a p73 target. Recombinant measles virus with an engineered deficiency in V protein is capable of inducing more severe cytopathic effects than the wild type, implicating measles virus V protein as an inhibitor of cell death. These findings also suggest that p73-PUMA signaling may be a previously unrecognized arm of cellular innate antiviral immunity.

* Corresponding author. Mailing address: Pancoe-ENH Research Pavilion, Northwestern University, 2200 Campus Dr., Evanston, IL 60208. Phone: (847) 491-5530. Fax: (847) 491-4400. E-mail: Horvath{at}northwestern.edu.

{dagger} C.D.C., H.P., and J.-P.P. contributed equally to this study.

Journal of Virology, June 2006, p. 5644-5650, Vol. 80, No. 11
0022-538X/06/$08.00+0     doi:10.1128/JVI.02400-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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