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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.

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.
Published ahead of print on 22 April 2009.
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