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Journal of Virology, July 2009, p. 6806-6816, Vol. 83, No. 13
0022-538X/09/$08.00+0     doi:10.1128/JVI.00263-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

A Viral Nonstructural Protein Regulates Bluetongue Virus Trafficking and Release

Cristina C. P. Celma and Polly Roy^*

Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom

Received 6 February 2009/ Accepted 2 April 2009

Bluetongue virus (BTV), a nonenveloped insect-borne virus, is released from infected cells by multiple pathways. Unlike other nonenveloped viruses, in addition to cell lysis the newly synthesized virus particles also appear to use a unique "budding" process. The nonstructural protein NS3, the only membrane protein encoded by BTV in infected cells, has been implicated in this process, since it appears to interact not only with the outermost viral capsid protein VP2 but also with a component of the cellular ESCRT pathway. However, to date it had not been possible to obtain direct evidence for the involvement of NS3 in BTV morphogenesis due to the lack of a genetic system that would allow introducing the targeted mutation in NS3 gene. In this study, we have used the recently developed T7 transcript-based reverse genetics system for BTV to introduce mutations in the sequence of NS3 into the viral genome and have investigated the effect of these mutations in the context of a replicating virus. While certain NS3 mutations exhibited drastic effects on newly synthesized virus release, others had less pronounced effects. In particular, mutations of two residues in the Tsg101 binding motif, the putative L domain of NS3, altered normal virus egress patterns and left nascent particles tethered to the cellular membrane, apparently arrested in the process of budding. In cells infected with a mutant virus that was incapable of an NS3-VP2 interaction, no budding particles were visualized. These data suggest that NS3 may act like the membrane protein of enveloped viruses and is responsible for intracellular trafficking and budding of virus particles. NS3 is thus a bridge between the maturing virion particles and cellular proteins during virus egress.

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* Corresponding author. Mailing address: London School of Hygiene and Tropical Medicine, Keppel St., London WC1E 7HT, United Kingdom. Phone: 44 (0)20-79272324. Fax: 44 (0)20-79272839. E-mail: polly.roy{at}lshtm.ac.uk

Published ahead of print on 15 April 2009.

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Journal of Virology, July 2009, p. 6806-6816, Vol. 83, No. 13
0022-538X/09/$08.00+0     doi:10.1128/JVI.00263-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

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