The nonstructural protein NSs of Schmallenberg virus is targeted to the nucleolus and induces nucleolar disorganization

Gouzil, J. et al. (2017) The nonstructural protein NSs of Schmallenberg virus is targeted to the nucleolus and induces nucleolar disorganization. Journal of Virology, 91(1), e01263-16. (doi: 10.1128/JVI.01263-16) (PMID:27795408) (PMCID:PMC5165206)

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Schmallenberg virus (SBV) was discovered in Germany in late 2011 and then spread rapidly to many European countries. SBV is an orthobunyavirus that causes abortion and congenital abnormalities in ruminants. A virus-encoded nonstructural protein, termed NSs, is a major virulence factor of SBV, and it is known to promote the degradation of Rpb1, a subunit of the RNA polymerase II (Pol II) complex, and therefore hampers global cellular transcription. In this study, we found that NSs is mainly localized in the nucleus of infected cells and specifically appears to target the nucleolus through a nucleolar localization signal (NoLS) localized between residues 33 and 51 of the protein. NSs colocalizes with nucleolar markers such as B23 (nucleophosmin) and fibrillarin. We observed that in SBV-infected cells, B23 undergoes a nucleolus-to-nucleoplasm redistribution, evocative of virus-induced nucleolar disruption. In contrast, the nucleolar pattern of B23 was unchanged upon infection with an SBV recombinant mutant with NSs lacking the NoLS motif (SBVΔNoLS). Interestingly, unlike wild-type SBV, the inhibitory activity of SBVΔNoLS toward RNA Pol II transcription is impaired. Overall, our results suggest that a putative link exists between NSs-induced nucleolar disruption and its inhibitory function on cellular transcription, which consequently precludes the cellular antiviral response and/or induces cell death.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Palmarini, Professor Massimo and Varela, Dr Mariana
Authors: Gouzil, J., Fablet, A., Lara, E., Caignard, G., Cochet, M., Kundlacz, C., Palmarini, M., Varela, M., Breard, E., Sailleau, C., Viarouge, C., Coulpier, M., Zientara, S., and Vitour, D.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Virology
Publisher:American Society for Microbiology
ISSN (Online):1098-5514
Published Online:19 October 2016
Copyright Holders:Copyright © 2016 Gouzil et al.
First Published:First published in Journal of Virology 91(1): e01263-16
Publisher Policy:Reproduced under a Creative Commons License

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