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Journal of Virology, December 1999, p. 9928-9933, Vol. 73, No. 12
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

The V Protein of Simian Virus 5 Inhibits Interferon Signalling by Targeting STAT1 for Proteasome-Mediated Degradation

L. Didcock,1 D. F. Young,1 S. Goodbourn,2 and R. E. Randall1,*

School of Biology, University of St. Andrews, Fife, Scotland KY16 9TS,1 and Department of Biochemistry, St. George's Hospital Medical School, University of London, London SW17 ORE,2 United Kingdom

Received 10 June 1999/Accepted 9 August 1999

To replicate in vivo, viruses must circumvent cellular antiviral defense mechanisms, including those induced by the interferons (IFNs). Here we demonstrate that simian virus 5 (SV5) blocks IFN signalling in human cells by inhibiting the formation of the IFN-stimulated gene factor 3 and gamma-activated factor transcription complexes that are involved in activating IFN-alpha /beta - and IFN-gamma -responsive genes, respectively. SV5 inhibits the formation of these complexes by specifically targeting STAT1, a component common to both transcription complexes, for proteasome-mediated degradation. Expression of the SV5 structural protein V, in the absence of other virus proteins, also inhibited IFN signalling and induced the degradation of STAT1. Following infection with SV5, STAT1 was degraded in the absence of virus protein synthesis and remained undetectable for up to 4 days postinfection. Furthermore, STAT1 was also degraded in IFN-pretreated cells, even though the cells were in an antiviral state. Since pretreatment of cells with IFN delayed but did not prevent virus replication and protein synthesis, these observations suggest that following infection of IFN-pretreated cells, SV5 remains viable within the cells until they eventually go out of the antiviral state.


* Corresponding author. Mailing address: Biomolecular Sciences Bldg., North Haugh, University of St. Andrews, Fife, Scotland KY16 9TS, United Kingdom. Phone: 44 1334 463397. Fax: 44 1334 462595. E-mail: rer{at}st-and.ac.uk.


Journal of Virology, December 1999, p. 9928-9933, Vol. 73, No. 12
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.



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Copyright © 1999 by the American Society for Microbiology. All rights reserved.