Dual Modulation of Type I Interferon Response by Bluetongue Virus

Doceul, Virginie; Chauveau, Emilie; Lara, Estelle; Bréard, Emmanuel; Sailleau, Corinne; Zientara, Stéphan; Vitour, Damien

doi:10.1128/jvi.01235-14

Cited by 19 publications

(21 citation statements)

References 52 publications

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“…BTV infection impairs ISRE promoter activation after IFN-I stimulation in A549 cells [32]. Using a dual-luciferase reporter gene assay with 293T cells, we confirmed that BTV infection also interfered with this signaling pathway in our model system ( Fig 1A).…”

Section: Btv Infection Suppresses Type I and Ii Ifn Signaling And Blosupporting

confidence: 70%

“…To our knowledge, our report is nonetheless the first description of a viral protein that uses its ubiquitination to degrade a host protein through autophagy. It has been previously shown that BTV evolved mechanisms to subvert the IFN-I response [32]. In our study, BTV counteracts the IFN-I response and interferes with IFN-I induction and IFN-II signaling.…”

Section: Discussionsupporting

confidence: 51%

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Virus‐induced autophagic degradation of STAT 2 as a mechanism for interferon signaling blockade

et al. 2019

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The mammalian interferon (IFN) signaling pathway is a primary component of the innate antiviral response, and viral pathogens have evolved multiple mechanisms to antagonize this pathway and to facilitate infection. Bluetongue virus (BTV), an orbivirus of the Reoviridae family, is transmitted by midges to ruminants and causes a disease that produces important economic losses and restriction to animal trade and is of compulsory notification to the World Organization for Animal Health (OIE). Here, we show that BTV interferes with IFN-I and IFN-II responses in two ways, by blocking STAT1 phosphorylation and by degrading STAT2. BTV-NS3 protein, which is involved in virion egress, interacts with STAT2, and induces its degradation by an autophagy-dependent mechanism. This STAT2 degradative process requires the recruitment of an E3-Ub-ligase to NS3 as well as NS3 K63 polyubiquitination. Taken together, our study identifies a new mechanism by which a virus degrades STAT2 for IFN signaling blockade, highlighting the diversity of mechanisms employed by viruses to subvert the IFN response.

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Section: Btv Infection Suppresses Type I and Ii Ifn Signaling And Blosupporting

confidence: 70%

Section: Discussionsupporting

confidence: 51%

Virus‐induced autophagic degradation of STAT 2 as a mechanism for interferon signaling blockade

et al. 2019

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“…Shamonda virus (SHAV) was kindly provided by Philippe Despres (Institut Pasteur, France). The wild-type field strain of bluetongue virus serotype 8 (BTV-8) was isolated in the department of Ardennes in 2006 (48). Infections were performed with subconfluent HeLa and CPT-Tert cells or hNPCs.…”

Section: Methodsmentioning

confidence: 99%

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

Gouzil

Fablet

Lara

et al. 2017

J Virol

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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.IMPORTANCE 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.

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“…Blue tongue virus, a segmented double stranded RNA virus, causes a severe disease in ruminants. The inhibition of the type 1 IFN response by blue tongue virus involves two different mechanisms [ 65 ]. During early infection (within 24 h in cell culture), the virus blocks the phosphorylation and nuclear translocation of STAT1; however, during late infection, the virus modulates the IFN-1 response by inducing the downregulation of JAK1 and Tyk2 protein expression [ 65 ].…”

Section: Targeting Tyk2 and Jak1 Ifn Receptor Associated Kinasesmentioning

confidence: 99%

Viral Inhibition of the IFN-Induced JAK/STAT Signalling Pathway: Development of Live Attenuated Vaccines by Mutation of Viral-Encoded IFN-Antagonists

Fleming

2016

Vaccines

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The interferon (IFN) induced anti-viral response is amongst the earliest and most potent of the innate responses to fight viral infection. The induction of the Janus kinase/signal transducer and activation of transcription (JAK/STAT) signalling pathway by IFNs leads to the upregulation of hundreds of interferon stimulated genes (ISGs) for which, many have the ability to rapidly kill viruses within infected cells. During the long course of evolution, viruses have evolved an extraordinary range of strategies to counteract the host immune responses in particular by targeting the JAK/STAT signalling pathway. Understanding how the IFN system is inhibited has provided critical insights into viral virulence and pathogenesis. Moreover, identification of factors encoded by viruses that modulate the JAK/STAT pathway has opened up opportunities to create new anti-viral drugs and rationally attenuated new generation vaccines, particularly for RNA viruses, by reverse genetics.

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Dual Modulation of Type I Interferon Response by Bluetongue Virus

Cited by 19 publications

References 52 publications

Virus‐induced autophagic degradation of STAT 2 as a mechanism for interferon signaling blockade

Virus‐induced autophagic degradation of STAT 2 as a mechanism for interferon signaling blockade

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

Viral Inhibition of the IFN-Induced JAK/STAT Signalling Pathway: Development of Live Attenuated Vaccines by Mutation of Viral-Encoded IFN-Antagonists

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