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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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  • Kubota, T., Yokosawa, N., Yokota, S.-i., Fujii, N. (2002). Association of Mumps Virus V Protein with RACK1 Results in Dissociation of STAT-1 from the Alpha Interferon Receptor Complex. J. Virol. 76: 12676-12682 [Abstract] [Full Text]  
  • Yokosawa, N., Yokota, S.-i., Kubota, T., Fujii, N. (2002). C-Terminal Region of STAT-1{alpha} Is Not Necessary for Its Ubiquitination and Degradation Caused by Mumps Virus V Protein. J. Virol. 76: 12683-12690 [Abstract] [Full Text]  
  • Neumann, G., Whitt, M. A., Kawaoka, Y. (2002). A decade after the generation of a negative-sense RNA virus from cloned cDNA - what have we learned?. J. Gen. Virol. 83: 2635-2662 [Abstract] [Full Text]  
  • Andrejeva, J., Poole, E., Young, D. F., Goodbourn, S., Randall, R. E. (2002). The p127 Subunit (DDB1) of the UV-DNA Damage Repair Binding Protein Is Essential for the Targeted Degradation of STAT1 by the V Protein of the Paramyxovirus Simian Virus 5. J. Virol. 76: 11379-11386 [Abstract] [Full Text]  
  • Rodriguez, J. J., Parisien, J.-P., Horvath, C. M. (2002). Nipah Virus V Protein Evades Alpha and Gamma Interferons by Preventing STAT1 and STAT2 Activation and Nuclear Accumulation. J. Virol. 76: 11476-11483 [Abstract] [Full Text]  
  • Wansley, E. K., Parks, G. D. (2002). Naturally Occurring Substitutions in the P/V Gene Convert the Noncytopathic Paramyxovirus Simian Virus 5 into a Virus That Induces Alpha/Beta Interferon Synthesis and Cell Death. J. Virol. 76: 10109-10121 [Abstract] [Full Text]  
  • Weber, F., Bridgen, A., Fazakerley, J. K., Streitenfeld, H., Kessler, N., Randall, R. E., Elliott, R. M. (2002). Bunyamwera Bunyavirus Nonstructural Protein NSs Counteracts the Induction of Alpha/Beta Interferon. J. Virol. 76: 7949-7955 [Abstract] [Full Text]  
  • Kato, A., Ohnishi, Y., Hishiyama, M., Kohase, M., Saito, S., Tashiro, M., Nagai, Y. (2002). The Amino-Terminal Half of Sendai Virus C Protein Is Not Responsible for either Counteracting the Antiviral Action of Interferons or Down-Regulating Viral RNA Synthesis. J. Virol. 76: 7114-7124 [Abstract] [Full Text]  
  • Parisien, J.-P., Lau, J. F., Horvath, C. M. (2002). STAT2 Acts as a Host Range Determinant for Species-Specific Paramyxovirus Interferon Antagonism and Simian Virus 5 Replication. J. Virol. 76: 6435-6441 [Abstract] [Full Text]  
  • Parisien, J.-P., Lau, J. F., Rodriguez, J. J., Ulane, C. M., Horvath, C. M. (2002). Selective STAT Protein Degradation Induced by Paramyxoviruses Requires both STAT1 and STAT2 but Is Independent of Alpha/Beta Interferon Signal Transduction. J. Virol. 76: 4190-4198 [Abstract] [Full Text]  
  • Bossert, B., Conzelmann, K.-K. (2002). Respiratory Syncytial Virus (RSV) Nonstructural (NS) Proteins as Host Range Determinants: a Chimeric Bovine RSV with NS Genes from Human RSV Is Attenuated in Interferon-Competent Bovine Cells. J. Virol. 76: 4287-4293 [Abstract] [Full Text]  
  • Andrejeva, J., Young, D. F., Goodbourn, S., Randall, R. E. (2002). Degradation of STAT1 and STAT2 by the V Proteins of Simian Virus 5 and Human Parainfluenza Virus Type 2, Respectively: Consequences for Virus Replication in the Presence of Alpha/Beta and Gamma Interferons. J. Virol. 76: 2159-2167 [Abstract] [Full Text]  
  • Zhirnov, O. P., Konakova, T. E., Wolff, T., Klenk, H.-D. (2002). NS1 Protein of Influenza A Virus Down-Regulates Apoptosis. J. Virol. 76: 1617-1625 [Abstract] [Full Text]  


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