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.
School of Biology,
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-
/
- and IFN-
-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.
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