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Journal of Virology, May 2009, p. 4942-4951, Vol. 83, No. 10
0022-538X/09/$08.00+0     doi:10.1128/JVI.01450-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Rotavirus Antagonizes Cellular Antiviral Responses by Inhibiting the Nuclear Accumulation of STAT1, STAT2, and NF-{kappa}B{triangledown}

Gavan Holloway,* Thanhmai T. Truong,{dagger} and Barbara S. Coulson

Department of Microbiology and Immunology, the University of Melbourne, Parkville, Victoria 3010, Australia

Received 11 July 2008/ Accepted 17 February 2009

A vital arm of the innate immune response to viral infection is the induction and subsequent antiviral effects of interferon (IFN). Rotavirus reduces type I IFN induction in infected cells by the degradation of IFN regulatory factors. Here, we show that the monkey rotavirus RRV and human rotavirus Wa also block gene expression induced by type I and II IFNs through a mechanism allowing signal transducer and activator of transcription 1 (STAT1) and STAT2 activation but preventing their nuclear accumulation. In infected cells, this may allow rotavirus to block the antiviral actions of IFN produced early in infection or by activated immune cells. As the intracellular expression of rotavirus nonstructural proteins NSP1, NSP3, and NSP4 individually did not inhibit IFN-stimulated gene expression, their involvement in this process is unlikely. RRV and Wa rotaviruses also prevented the tumor necrosis factor alpha-stimulated nuclear accumulation of NF-{kappa}B and NF-{kappa}B-driven gene expression. In addition, NF-{kappa}B was activated by rotavirus infection, confirming earlier findings by others. As NF-{kappa}B is important for the induction of IFN and other cytokines during viral infection, this suggests that rotavirus prevents cellular transcription as a means to evade host responses. To our knowledge, this is the first report of the use of this strategy by a double-stranded RNA virus.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, the University of Melbourne, Parkville, Victoria 3010, Australia. Phone: 61 3 8344 5715. Fax: 61 3 9347 1540. E-mail: hollg{at}unimelb.edu.au

{triangledown} Published ahead of print on 25 February 2009.

{dagger} Present address: Department of Zoology, The University of Melbourne, Victoria 3010, Australia.

Journal of Virology, May 2009, p. 4942-4951, Vol. 83, No. 10
0022-538X/09/$08.00+0     doi:10.1128/JVI.01450-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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