Identification and characterization of a novel non-structural protein of bluetongue virus

Ratinier, M. et al. (2011) Identification and characterization of a novel non-structural protein of bluetongue virus. PLoS Pathogens, 7(12), e1002477. (doi: 10.1371/journal.ppat.1002477) (PMID:22241985) (PMCID:PMC3248566)

Abstract

Bluetongue virus (BTV) is the causative agent of a major disease of livestock (bluetongue). For over two decades, it has been widely accepted that the 10 segments of the dsRNA genome of BTV encode for 7 structural and 3 non-structural proteins. The non-structural proteins (NS1, NS2, NS3/NS3a) play different key roles during the viral replication cycle. In this study we show that BTV expresses a fourth non-structural protein (that we designated NS4) encoded by an open reading frame in segment 9 overlapping the open reading frame encoding VP6. NS4 is 77–79 amino acid residues in length and highly conserved among several BTV serotypes/strains. NS4 was expressed early post-infection and localized in the nucleoli of BTV infected cells. By reverse genetics, we showed that NS4 is dispensable for BTV replication in vitro, both in mammalian and insect cells, and does not affect viral virulence in murine models of bluetongue infection. Interestingly, NS4 conferred a replication advantage to BTV-8, but not to BTV-1, in cells in an interferon (IFN)-induced antiviral state. However, the BTV-1 NS4 conferred a replication advantage both to a BTV-8 reassortant containing the entire segment 9 of BTV-1 and to a BTV-8 mutant with the NS4 identical to the homologous BTV-1 protein. Collectively, this study suggests that NS4 plays an important role in virus-host interaction and is one of the mechanisms played, at least by BTV-8, to counteract the antiviral response of the host. In addition, the distinct nucleolar localization of NS4, being expressed by a virus that replicates exclusively in the cytoplasm, offers new avenues to investigate the multiple roles played by the nucleolus in the biology of the cell.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Shaw, Dr Andrew and Caporale, Dr Marco and Ratinier, Dr Maxime and Palmarini, Professor Massimo and Allan, Dr Kathryn and Golder, Mr Matthew and Rixon, Dr Frazer and Fernandes Nunes, Dr Sandro Filipe
• Authors: Ratinier, M., Caporale, M., Golder, M., Franzoni, G., Allan, K., Nunes, S.F., Armezzani, A., Bayoumy, A., Rixon, F., Shaw, A., and Palmarini, M.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research; College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
• Journal Name: PLoS Pathogens
• Publisher: Public Library of Science
• ISSN: 1553-7366
• ISSN (Online): 1553-7374
• Published Online: 29 December 2011
• Copyright Holders: Copyright © 2011 The Authors
• First Published: First published in PLoS Pathogens 7(12):e1002477
• Publisher Policy: Reproduced under a Creative Commons Licence

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
65653	1	Structural studies on human viruses	Frazer Rixon	Medical Research Council (MRC)	MC_UU_12014/6	MVLS III - CENTRE FOR VIRUS RESEARCH