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Journal ArticleDOI

Newcastle disease virus (NDV)-based assay demonstrates interferon-antagonist activity for the NDV V protein and the Nipah virus V, W, and C proteins.

15 Jan 2003-Journal of Virology (American Society for Microbiology)-Vol. 77, Iss: 2, pp 1501-1511
TL;DR: It is shown that expression of the NDV V protein or the Nipah virus V, W, or C proteins rescues NDV-GFP replication in the face of the transfection-induced IFN response, and that the NDVs could be used to screen proteins expressed from plasmids for the ability to counteract the host cellIFN response.
Abstract: We have generated a recombinant Newcastle disease virus (NDV) that expresses the green fluorescence protein (GFP) in infected chicken embryo fibroblasts (CEFs). This virus is interferon (IFN) sensitive, and pretreatment of cells with chicken alpha/beta IFN (IFN-α/β) completely blocks viral GFP expression. Prior transfection of plasmid DNA induces an IFN response in CEFs and blocks NDV-GFP replication. However, transfection of known inhibitors of the IFN-α/β system, including the influenza A virus NS1 protein and the Ebola virus VP35 protein, restores NDV-GFP replication. We therefore conclude that the NDV-GFP virus could be used to screen proteins expressed from plasmids for the ability to counteract the host cell IFN response. Using this system, we show that expression of the NDV V protein or the Nipah virus V, W, or C proteins rescues NDV-GFP replication in the face of the transfection-induced IFN response. The V and W proteins of Nipah virus, a highly lethal pathogen in humans, also block activation of an IFN-inducible promoter in primate cells. Interestingly, the amino-terminal region of the Nipah virus V protein, which is identical to the amino terminus of Nipah virus W, is sufficient to exert the IFN-antagonist activity. In contrast, the anti-IFN activity of the NDV V protein appears to be located in the carboxy-terminal region of the protein, a region implicated in the IFN-antagonist activity exhibited by the V proteins of mumps virus and human parainfluenza virus type 2.
Citations
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Journal ArticleDOI
TL;DR: Applied aspects that arise from an increase in knowledge in this area are described, including vaccine design and manufacture, the development of novel antiviral drugs and the use of IFN-sensitive oncolytic viruses in the treatment of cancer.
Abstract: The interferon (IFN) system is an extremely powerful antiviral response that is capable of controlling most, if not all, virus infections in the absence of adaptive immunity. However, viruses can still replicate and cause disease in vivo, because they have some strategy for at least partially circumventing the IFN response. We reviewed this topic in 2000 [Goodbourn, S., Didcock, L. & Randall, R. E. (2000). J Gen Virol 81, 2341-2364] but, since then, a great deal has been discovered about the molecular mechanisms of the IFN response and how different viruses circumvent it. This information is of fundamental interest, but may also have practical application in the design and manufacture of attenuated virus vaccines and the development of novel antiviral drugs. In the first part of this review, we describe how viruses activate the IFN system, how IFNs induce transcription of their target genes and the mechanism of action of IFN-induced proteins with antiviral action. In the second part, we describe how viruses circumvent the IFN response. Here, we reflect upon possible consequences for both the virus and host of the different strategies that viruses have evolved and discuss whether certain viruses have exploited the IFN response to modulate their life cycle (e.g. to establish and maintain persistent/latent infections), whether perturbation of the IFN response by persistent infections can lead to chronic disease, and the importance of the IFN system as a species barrier to virus infections. Lastly, we briefly describe applied aspects that arise from an increase in our knowledge in this area, including vaccine design and manufacture, the development of novel antiviral drugs and the use of IFN-sensitive oncolytic viruses in the treatment of cancer.

1,564 citations

Journal ArticleDOI
TL;DR: This work reports that the influenza A virus nonstructural protein 1 (NS1) specifically inhibits TRIM25-mediated RIG-I CARD ubiquitination, thereby suppressing Rig-I signal transduction and revealing a mechanism by which influenza virus inhibits host IFN response.

765 citations


Cites methods from "Newcastle disease virus (NDV)-based..."

  • ...Therefore, we measured IFN production from infected A549 cells by bioassay (Park et al., 2003; Solorzano et al., 2005)....

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  • ...Interferon produced from cells infected with the indicated influenza viruses at an MOI of 2 was examined by an interferon bioassay as described elsewhere (Park et al., 2003; Quinlivan et al., 2005; Solorzano et al., 2005)....

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Journal ArticleDOI
30 Jan 2014-Nature
TL;DR: Comparative analysis reveals that the screened ISGs target positive-sense single-stranded RNA viruses more effectively than negative-sensesingle-strander RNA viruses.
Abstract: The type I interferon (IFN) response protects cells from viral infection by inducing hundreds of interferon-stimulated genes (ISGs), some of which encode direct antiviral effectors. Recent screening studies have begun to catalogue ISGs with antiviral activity against several RNA and DNA viruses. However, antiviral ISG specificity across multiple distinct classes of viruses remains largely unexplored. Here we used an ectopic expression assay to screen a library of more than 350 human ISGs for effects on 14 viruses representing 7 families and 11 genera. We show that 47 genes inhibit one or more viruses, and 25 genes enhance virus infectivity. Comparative analysis reveals that the screened ISGs target positive-sense single-stranded RNA viruses more effectively than negative-sense single-stranded RNA viruses. Gene clustering highlights the cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS, also known as MB21D1) as a gene whose expression also broadly inhibits several RNA viruses. In vitro, lentiviral delivery of enzymatically active cGAS triggers a STING-dependent, IRF3-mediated antiviral program that functions independently of canonical IFN/STAT1 signalling. In vivo, genetic ablation of murine cGAS reveals its requirement in the antiviral response to two DNA viruses, and an unappreciated contribution to the innate control of an RNA virus. These studies uncover new paradigms for the preferential specificity of IFN-mediated antiviral pathways spanning several virus families.

765 citations

Journal ArticleDOI
05 Jan 2006-Virology
TL;DR: The current view on the balancing act between virus-induced IFN responses and the viral counterplayers is discussed.

667 citations


Additional excerpts

  • ...The following viral IFN antagonists are shown in clockwise order: NS1 of FLUAV (Garcia-Sastre, 2001; Garcia-Sastre et al., 1998; Talon et al., 2000a; Wang et al., 2000) , NS1 of FLUBV (Dauber et al., 2004) , E3L VV (Smith et al., 2001; Xiang et al., 2002) , V of paramyxoviruses , NS3/4A of HCV (Breiman et al., 2005; , VP35 of EBOV , P of RV , P of BDV (Unterstab et al., in press) , V, W of Nipah virus (Park et al., 2003; Shaw et al., 2004) , NS1/NS2 of RSV (Bossert et al., 2003; Spann et al., 2004; Valarcher et al., 2003) , leader protein of TMEV (Delhaye et al., 2004; van Pesch et al., 2001 ), ML of THOV (Hagmaier, 2003 Jennings, 2004 #233; Pichlmair, 2004 #247) , NPro of CSFV (La Rocca et al., 2005; Ruggli et al., 2003 Ruggli et al., , 2005 , vIRF and ORF45 of HHV-8 (Burysek et al., 1999a (Burysek et al., , 1999b Li et al., 1998; Lubyova et al., 2004; Lubyova and Pitha, 2000; Zhu et al., 2002; Zimring et al., 1998) , E6 of HPV16 , BZLF-1 of EBV (Hahn et al., 2005) , M of VSV (Ahmed et al., 2003; Yuan et al., 1998) , 3C Pro of PV (Clark et al., 1993; Yalamanchili et al., 1996) , NSs of BUNV (Thomas et al., 2004; Weber et al., 2002) , NSs of RVFV, Bouloy et al., 2001; Le May et al., 2004) , B18 and B8 of VV (Alcami et al., 2000; Symons et al., 1995) , JEV, WNV (Guo et al., 2005; Lin et al., 2004) , E6 of HPV18 , core protein of HCV (Bode et al., 2003; Keskinen et al., 2002; Melen et al., 2004; Miller et al., 2004) , HSV-1 (Yokota et al., 2004) , NSs of RVFV (M. Bouloy, pers....

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Journal ArticleDOI
TL;DR: It has been determined that SARS-CoV open reading frame (ORF) 3b, ORF 6, and N proteins antagonize interferon, a key component of the innate immune response.
Abstract: The severe acute respiratory syndrome coronavirus (SARS-CoV) is highly pathogenic in humans, with a death rate near 10%. This high pathogenicity suggests that SARS-CoV has developed mechanisms to overcome the host innate immune response. It has now been determined that SARS-CoV open reading frame (ORF) 3b, ORF 6, and N proteins antagonize interferon, a key component of the innate immune response. All three proteins inhibit the expression of beta interferon (IFN-beta), and further examination revealed that these SARS-CoV proteins inhibit a key protein necessary for the expression of IFN-beta, IRF-3. N protein dramatically inhibited expression from an NF-kappaB-responsive promoter. All three proteins were able to inhibit expression from an interferon-stimulated response element (ISRE) promoter after infection with Sendai virus, while only ORF 3b and ORF 6 proteins were able to inhibit expression from the ISRE promoter after treatment with interferon. This indicates that N protein inhibits only the synthesis of interferon, while ORF 3b and ORF 6 proteins inhibit both interferon synthesis and signaling. ORF 6 protein, but not ORF 3b or N protein, inhibited nuclear translocation but not phosphorylation of STAT1. Thus, it appears that these three interferon antagonists of SARS-CoV inhibit the interferon response by different mechanisms.

628 citations

References
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Journal ArticleDOI
15 Dec 1991-Gene
TL;DR: The results showed that high concentrations of G418 efficiently yielded L cell and CHO cell transfectants stably producing IL-2 at levels comparable with those previously attained using gene amplification.

4,971 citations


"Newcastle disease virus (NDV)-based..." refers methods in this paper

  • ...All ORFs were cloned into the mammalian expression plasmid pCAGGS ( 44 )....

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Journal ArticleDOI
26 May 2000-Science
TL;DR: Electron microscopic, serologic, and genetic studies indicate that the Nipah virus belongs to the family Paramyxoviridae and is most closely related to the recently discovered Hendra virus, and it is suggested that these two viruses are representative of a new genus within the familyparamyxviridae.
Abstract: A paramyxovirus virus termed Nipah virus has been identified as the etiologic agent of an outbreak of severe encephalitis in people with close contact exposure to pigs in Malaysia and Singapore. The outbreak was first noted in late September 1998 and by mid-June 1999, more than 265 encephalitis cases, including 105 deaths, had been reported in Malaysia, and 11 cases of encephalitis or respiratory illness with one death had been reported in Singapore. Electron microscopic, serologic, and genetic studies indicate that this virus belongs to the family Paramyxoviridae and is most closely related to the recently discovered Hendra virus. We suggest that these two viruses are representative of a new genus within the family Paramyxoviridae. Like Hendra virus, Nipah virus is unusual among the paramyxoviruses in its ability to infect and cause potentially fatal disease in a number of host species, including humans.

1,108 citations


"Newcastle disease virus (NDV)-based..." refers background or methods in this paper

  • ...We further use this assay to show that the V, W, and C proteins of Nipah virus, an important emerging pathogen that is highly lethal in humans (9, 14, 34), also exhibit IFN-antagonist activity....

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  • ...Nipah virus was chosen because of its importance as an emerging paramyxovirus that causes severe disease in humans (9)....

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Journal ArticleDOI
20 Dec 1998-Virology
TL;DR: In this paper, a viable transfectant influenza A virus (delNS1) which lacks the NS1 gene has been generated through the use of reverse genetics, and it has been shown that the NS 1 protein plays a crucial role in inhibiting interferon-mediated antiviral responses of the host.

998 citations