The Ebola Virus VP35 Protein Inhibits Activation of Interferon Regulatory Factor 3

Basler, Christopher F.; Mikulasova, Andrea; Martínez-Sobrido, Luis; Paragas, Jason; Mühlberger, Elke; Bray, Mike; Klenk, Hans‐Dieter; Palese, Peter; Garcı́a-Sastre, Adolfo

doi:10.1128/jvi.77.14.7945-7956.2003

Cited by 431 publications

(385 citation statements)

References 92 publications

(144 reference statements)

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“…Although its early history is unclear, this strain has been used extensively in type I IFN research (15)(16)(17)(18) and for the production of purified IFN-␣ (19). Investigations from our laboratory demonstrated that SeV-C is a much stronger inducer of both DC maturation and type I IFN production than SeV-52 or influenza virus (5).…”

mentioning

confidence: 91%

A Novel Role for Viral-Defective Interfering Particles in Enhancing Dendritic Cell Maturation

Yount

Kraus

Horvath

et al. 2006

The Journal of Immunology

109

152

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Dendritic cell (DC) maturation is a crucial event in the development of adaptive immune responses that confer long-lasting protection against reinfection with the same virus. Sendai virus strain Cantell has a particularly strong ability to mature DCs independently of type I IFNs and TLR signaling, currently the best-described pathways for the induction of DC maturation. In this study, we demonstrate that defective-interfering (DI) particles present in Sendai virus-Cantell stocks are required for its robust DC maturation ability. DI particles contain incomplete genomes that are unable to replicate unless the viral polymerase is supplied by coinfection with complete virus. Accordingly, the improvement in the virus-induced maturation of DCs provided by DI particles requires standard virus coinfection and likely results from increased production of dsRNA replication intermediaries. This unique ability of DI particles to stimulate DC maturation cannot be mimicked by simply increasing the dose of standard virus. Furthermore, viruses with weak DC maturation abilities can be converted into potent DC stimulators with the addition of DI particles, supporting a potential application for DI particles as a novel natural adjuvant for viral immunizations.

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mentioning

confidence: 91%

A Novel Role for Viral-Defective Interfering Particles in Enhancing Dendritic Cell Maturation

Yount

Kraus

Horvath

et al. 2006

The Journal of Immunology

109

152

View full text Add to dashboard Cite

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“…The IFN␤ promoter construct, pGL3/IFN␤p-Luc, was described previously (36). The expression plasmids IRF7 (35), FLAG-IRF7 and its mutants (36), IRF3 and IRF3(5D), were described previously (29). The zinc inducible kinase inactive Jak1 (Jak1 K896R) cDNA cloned in MTCB6ϩ vector was kindly provided by Paul Rothman (37).…”

Section: Methodsmentioning

confidence: 99%

Regulation of the Transcriptional Activity of the IRF7 Promoter by a Pathway Independent of Interferon Signaling

Ning

Huye

Pagano

2005

Journal of Biological Chemistry

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“…It has been demonstrated that many viral IFN antagonists interfere with the IRF-3 and/or NF-kB signalling pathways (Basler et al, 2003;Boxer et al, 2009;Kochs et al, 2007;Kopecky-Bromberg et al, 2007). We next determined the impact of Nsp2 expression on the IRF-3-or NF-kBdependent, SeV-induced activation of the IFN-b promoter.…”

Section: Nsp2 Inhibits the Activation Of Irf-3-and Nf-kbresponsive Prmentioning

confidence: 99%

The cysteine protease domain of porcine reproductive and respiratory syndrome virus non-structural protein 2 antagonizes interferon regulatory factor 3 activation

Zheng

Zhou

et al. 2010

Journal of General Virology

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There is growing evidence that porcine reproductive and respiratory syndrome virus (PRRSV) has developed mechanisms to subvert the host innate immune response. PRRSV non-structural protein 2 (Nsp2) was suggested previously as a potential interferon (IFN) antagonist. This study focused on Nsp2 to investigate its inhibitory mechanism of IFN induction. It was demonstrated that Nsp2 strongly inhibited IFN-b production by antagonizing activation of the IFN regulatory factor 3 (IRF-3) pathway induced by the Sendai virus (SeV). Further studies revealed that the cysteine protease domain (PL2) of Nsp2 was necessary for IFN antagonism. Additionally, both full-length Nsp2 and the PL2 protease domain of Nsp2 were found to inhibit SeV-induced phosphorylation and nuclear translocation of IRF-3. These findings suggest that Nsp2 is likely to play an important role in subversion of IRF-3-dependent innate antiviral defences, providing a basis for elucidating the mechanisms underlying PRRSV pathogenesis. INTRODUCTIONThe production of type I interferons (IFN-a/b) plays a pivotal role in the host antiviral immune defence (Bonjardim, 2005). Cellular sensors capable of recognizing various viral determinants initiate IFN signal transduction. Positive-stranded RNA viruses can generate intermediate dsRNA during replication, which is an efficient inducer of type I IFNs. This intermediate dsRNA can trigger a cascade of cellular sensors, resulting in type I IFN production and secretion (Kawai & Akira, 2006a;Randall & Goodbourn, 2008). The induction of type I IFNs is initiated via recognition of a pathogen-associated molecule in dsRNA by cellular pattern recognition receptors, including Tolllike receptor 3 (TLR3), caspase recruitment domain (CARD)-containing proteins, retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 . TLR3 signals through the adaptor molecule Toll-interleukin-1-resistance domain-containing adaptor inducing IFN-b (TRIF), whilst MDA-5 and RIG-I signal through the adaptor molecule mitochondrial antiviral signal protein (MAVS; also known as IPS-1, Cardif and VISA) to activate a type I IFN response (Kawai & Akira, 2006b; Kawai et al., 2005; Yamamoto et al., 2003). Despite utilizing different adaptors, both pathways converge to activate two downstream kinases, TANK-binding kinase 1 (TBK-1) and inhibitor of kB kinase e (IKKe), subsequently leading to the activation of latent IFN transcription factors, including IFN regulatory factors (IRF-3 and/or IRF-7), nuclear factor-kB (NF-kB) and activating protein 1 (AP-1) (Fitzgerald et al., 2003;Randall & Goodbourn, 2008; Sharma et al., 2003). Activated IFN transcription factors translocate to the nucleus and activate IFN transcription (Biron, 2001). Secreted IFN binds to the IFN receptor and activates a JAK/STAT signalling pathway, upregulating the expression of a subset of genes that impede virus replication (Randall & Goodbourn, 2008). However, many viruses have evolved mechanisms to circumvent the IFN response (Blakqori et al., 2007;Jennings et al.,...

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The Ebola Virus VP35 Protein Inhibits Activation of Interferon Regulatory Factor 3

Cited by 431 publications

References 92 publications

A Novel Role for Viral-Defective Interfering Particles in Enhancing Dendritic Cell Maturation

A Novel Role for Viral-Defective Interfering Particles in Enhancing Dendritic Cell Maturation

Regulation of the Transcriptional Activity of the IRF7 Promoter by a Pathway Independent of Interferon Signaling

The cysteine protease domain of porcine reproductive and respiratory syndrome virus non-structural protein 2 antagonizes interferon regulatory factor 3 activation

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