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Journal of Virology, June 2009, p. 5735-5748, Vol. 83, No. 11
0022-538X/09/$08.00+0     doi:10.1128/JVI.02440-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Cell-to-Cell Spread of the RNA Interference Response Suppresses Semliki Forest Virus (SFV) Infection of Mosquito Cell Cultures and Cannot Be Antagonized by SFV{triangledown}

Ghassem Attarzadeh-Yazdi,1,{dagger} Rennos Fragkoudis,1,{dagger} Yi Chi,1 Ricky W. C. Siu,1 Liane Ülper,2 Gerald Barry,1 Julio Rodriguez-Andres,1 Anthony A. Nash,1 Michèle Bouloy,3 Andres Merits,2 John K. Fazakerley,1 and Alain Kohl1*

The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Summerhall, Edinburgh EH9 1QH, Scotland, United Kingdom,1 Institute of Technology, University of Tartu, Nooruse 1, Tartu 50411, Estonia,2 Unité de Génétique Moléculaire des Bunyaviridés, Institut Pasteur, 25 Rue du Dr. Roux, 75724 Paris 15, France3

Received 26 November 2008/ Accepted 12 March 2009

In their vertebrate hosts, arboviruses such as Semliki Forest virus (SFV) (Togaviridae) generally counteract innate defenses and trigger cell death. In contrast, in mosquito cells, following an early phase of efficient virus production, a persistent infection with low levels of virus production is established. Whether arboviruses counteract RNA interference (RNAi), which provides an important antiviral defense system in mosquitoes, is an important question. Here we show that in Aedes albopictus-derived mosquito cells, SFV cannot prevent the establishment of an antiviral RNAi response or prevent the spread of protective antiviral double-stranded RNA/small interfering RNA (siRNA) from cell to cell, which can inhibit the replication of incoming virus. The expression of tombusvirus siRNA-binding protein p19 by SFV strongly enhanced virus spread between cultured cells rather than virus replication in initially infected cells. Our results indicate that the spread of the RNAi signal contributes to limiting virus dissemination.


* Corresponding author. Mailing address: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Summerhall, Edinburgh EH9 1QH, Scotland, United Kingdom. Phone: 44 (0)131 651 3907. Fax: 44 (0)131 650 6511. E-mail: Alain.Kohl{at}ed.ac.uk

{triangledown} Published ahead of print on 18 March 2009.

{dagger} G.A.-Y. and R.F. contributed equally.


Journal of Virology, June 2009, p. 5735-5748, Vol. 83, No. 11
0022-538X/09/$08.00+0     doi:10.1128/JVI.02440-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.