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Journal of Virology, July 2009, p. 6347-6356, Vol. 83, No. 13
0022-538X/09/$08.00+0     doi:10.1128/JVI.00596-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

A Point Mutation, E95D, in the Mumps Virus V Protein Disengages STAT3 Targeting from STAT1 Targeting{triangledown}

Mamta Puri,1 Ken Lemon,2 W. Paul Duprex,2 Bertus K. Rima,2 and Curt M. Horvath1*

Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 60208-3500,1 School of Biomedical Sciences, The Queen's University of Belfast, 97 Lisburn Road, Belfast, United Kingdom BT9 7BL2

Received 23 March 2009/ Accepted 17 April 2009

Mumps virus, like other paramyxoviruses in the Rubulavirus genus, encodes a V protein that can assemble a ubiquitin ligase complex from cellular components, leading to the destruction of cellular signal transducer and activator of transcription (STAT) proteins. While many V proteins target the interferon-activated STAT1 or STAT2 protein, mumps virus V protein is unique in its ability to also target STAT3 for ubiquitin modification and proteasome-mediated degradation. Here we report that a single amino acid substitution in the mumps virus V protein, E95D, results in defective STAT3 targeting while maintaining the ability to target STAT1. Results indicate that the E95D mutation disrupts the ability of the V protein to associate with STAT3. A recombinant mumps virus carrying the E95D mutation in its P and V proteins replicates normally in cultured cells but fails to induce targeting of STAT3. Infection with the recombinant virus results in the differential regulation of a number of cellular genes compared to wild-type mumps virus and increases cell death in infected cells, producing a large-plaque phenotype.


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

{triangledown} Published ahead of print on 22 April 2009.


Journal of Virology, July 2009, p. 6347-6356, Vol. 83, No. 13
0022-538X/09/$08.00+0     doi:10.1128/JVI.00596-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.




This article has been cited by other articles:

  • Young, D. F., Galiano, M. C., Lemon, K., Chen, Y.-H., Andrejeva, J., Duprex, W. P., Rima, B. K., Randall, R. E. (2009). Mumps virus Enders strain is sensitive to interferon (IFN) despite encoding a functional IFN antagonist. J. Gen. Virol. 90: 2731-2738 [Abstract] [Full Text]