Nonstructural Protein NSs of Schmallenberg Virus Is Targeted to the Nucleolus and Induces Nucleolar Disorganization

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...

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Published in:Journal of virology 2017-01, Vol.91 (1)
Main Authors: Gouzil, Julie, Fablet, Aurore, Lara, Estelle, Caignard, Grégory, Cochet, Marielle, Kundlacz, Cindy, Palmarini, Massimo, Varela, Mariana, Breard, Emmanuel, Sailleau, Corinne, Viarouge, Cyril, Coulpier, Muriel, Zientara, Stéphan, Vitour, Damien
Format: Article
Language:English
Subjects:
Animals
Arbovirus
Bunyaviridae
Cell Line, Transformed
Cell Nucleolus - metabolism
Cell Nucleolus - ultrastructure
Cell Nucleolus - virology
Choroid Plexus - cytology
Choroid Plexus - metabolism
Choroid Plexus - virology
Chromosomal Proteins, Non-Histone - genetics
Chromosomal Proteins, Non-Histone - metabolism
Ependymoglial Cells - metabolism
Ependymoglial Cells - ultrastructure
Ependymoglial Cells - virology
Gene Expression Regulation
HeLa Cells
Host-Pathogen Interactions
Humans
Life Sciences
Mutation
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
Orthobunyavirus
Orthobunyavirus - genetics
Orthobunyavirus - metabolism
Orthobunyavirus - pathogenicity
Protein Sorting Signals
Protein Transport
Proteolysis
RNA Polymerase II - chemistry
RNA Polymerase II - genetics
RNA Polymerase II - metabolism
Ruminantia
Sheep
Signal Transduction
Transcription, Genetic
Viral Nonstructural Proteins - chemistry
Viral Nonstructural Proteins - genetics
Viral Nonstructural Proteins - metabolism
Virus-Cell Interactions
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Summary: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. Schmallenberg virus (SBV) is an emerging arbovirus of ruminants that spread in Europe between 2011 and 2013. SBV induces fetal abnormalities during gestation, with the central nervous system being one of the most affected organs. The virus-encoded NSs protein acts as a virulence factor by impairing host cell transcription. Here, we show that NSs contains a nucleolar localization signal (NoLS) and induces disorganization of the nucleolus. The NoLS motif in the SBV NSs is absolutely necessary for virus-induced inhibition of cellular transcription. To our knowledge, this is the first report of nucleolar functions for NSs within the Bunyaviridae family.
ISSN:0022-538X
1098-5514
DOI:10.1128/JVI.01263-16