Newcastle Disease Virus (NDV)-Based Assay Demonstrates Interferon-Antagonist Activity for the NDV V Protein and the Nipah Virus V, W, and C Proteins

Park, Man Seong; Shaw, Megan L.; Muñoz‐Jordán, Jorge L.; Cros, Jérôme; Nakaya, Takaaki; Bouvier, Nicole M.; Palese, Peter; Garcı́a-Sastre, Adolfo; Basler, Christopher F.

doi:10.1128/jvi.77.2.1501-1511.2003

Cited by 344 publications

(377 citation statements)

References 60 publications

(85 reference statements)

Supporting

Mentioning

363

Contrasting

Unclassified

Order By: Relevance

“…Instead, the minimal peptide region capable of STAT1 binding and IFN evasion maps to aa 100 to 160 and provides a mechanistic explanation for the observed rescue of an IFN-sensitive reporter virus and IFN signaling suppression conferred by the common N-termini of V and W proteins (21). The Henipavirus proteins, P and W, which are translated from partially overlapping open reading frames, share the same 406-aa N terminus prior to the editing site.…”

Section: Discussionmentioning

confidence: 99%

“…In comparison to the STAT-degrading Rubulavirus V proteins, the V proteins of Nipah virus and Hendra virus, the two known Henipavirus species, share approximately 55% amino acid identity within the CTD. Despite this CTD conservation, it is dispensable for IFN signaling inhibition (21). The Henipavirus V protein N terminus is entirely unique compared to other paramyxovirus proteomes, and the V proteins have no obvious homology to any cellular protein.…”

mentioning

confidence: 99%

“…As an IFN response modifier, the V protein is a virulence and pathogenesis-determining factor. In the case of SV5, species-specific restriction of STAT1 degradation has been shown to be a determinant of host species tropism, restricting SV5 replication in IFN-competent murine cells (20,31).A new genus of recently emerged paramyxoviruses, Henipavirus, was demonstrated to share V-dependent IFN signaling evasion properties with other paramyxoviruses (21,24,25). Encoded by a polycistronic gene, the 405-amino-acid V protein N terminus is shared with the co-amino-terminal P and W proteins (3).…”

mentioning

confidence: 99%

“…A new genus of recently emerged paramyxoviruses, Henipavirus, was demonstrated to share V-dependent IFN signaling evasion properties with other paramyxoviruses (21,24,25). Encoded by a polycistronic gene, the 405-amino-acid V protein N terminus is shared with the co-amino-terminal P and W proteins (3).…”

mentioning

confidence: 99%

See 3 more Smart Citations

Identification of the Nuclear Export Signal and STAT-Binding Domains of the Nipah Virus V Protein Reveals Mechanisms Underlying Interferon Evasion

Rodriguez

Cruz

Horvath

2004

J Virol

123

View full text Add to dashboard Cite

The V proteins of Nipah virus and Hendra virus have been demonstrated to bind to cellular STAT1 and STAT2 proteins to form high-molecular-weight complexes that inhibit interferon (IFN)-induced antiviral transcription by preventing STAT nuclear accumulation. Analysis of the Nipah virus V protein has revealed a region between amino acids 174 and 192 that functions as a CRM1-dependent nuclear export signal (NES).This peptide is sufficient to complement an export-defective human immunodeficiency virus Rev protein, and deletion and substitution mutagenesis revealed that this peptide is necessary for both V protein shuttling and cytoplasmic retention of STAT1 and STAT2 proteins. However, the NES is not required for V-dependent IFN signaling inhibition. IFN signaling is blocked primarily by interaction between Nipah virus V residues 100 to 160 and STAT1 residues 509 to 712. Interaction with STAT2 requires a larger Nipah virus V segment between amino acids 100 and 300, but deletion of residues 230 to 237 greatly reduced STAT2 coprecipitation. Further, V protein interactions with cellular STAT1 is a prerequisite for STAT2 binding, and sequential immunoprecipitations demonstrate that V, STAT1, and STAT2 can form a tripartite complex. These findings characterize essential regions for Henipavirus V proteins that represent potential targets for therapeutic intervention.The biological effects of alpha and beta interferon (IFN-␣ and -␤) are mediated by a transcription factor complex, ISGF3, that is comprised of the signal transducer and activator of transcription (STAT) proteins, STAT1 and STAT2, in association with a DNA-binding subunit, an IFN regulatory factor, IRF9 (1, 12). IFN-induced, ISGF3-mediated transcription results in a cellular antiviral state that provides protection against a broad range of virus types. In response to this negative selection, most viruses have evolved adaptations that allow them to evade IFN-induced innate antiviral responses (13,26).In the case of the paramyxovirus family of negative-strand RNA viruses, IFN signaling to ISGF3 is disrupted by direct targeting of STAT proteins (4). Current evidence from the study of several family members indicates that the common outcome of STAT targeting and IFN evasion is achieved by individual paramyxovirus species through a diverse range of molecular mechanisms. For example, the Rubulaviruses, simian virus 5 (SV5), human parainfluenza virus 2, and mumps virus all encode STAT-directed E3 ubiquitin ligase activities that function in combination with cellular proteins to target STAT1, STAT2, or STAT3 for proteasomal degradation (5,18,19,28,29). Distinctly, measles virus, a prototype Morbillivirus, does not induce STAT ubiquitylation and degradation but instead prevents IFN-induced ISGF3 assembly and STAT protein nuclear translocation (17, 27). These IFN evasion mechanisms rely on protein-protein interactions between STATs and the paramyxovirus-encoded V protein. The paramyxovirus V protein is characterized by a highly conserved cysteine-rich C-terminal domain (...

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Identification of the Nuclear Export Signal and STAT-Binding Domains of the Nipah Virus V Protein Reveals Mechanisms Underlying Interferon Evasion

Rodriguez

Cruz

Horvath

2004

J Virol

123

View full text Add to dashboard Cite

show abstract

“…Taken together these results suggest that the major effect of IFN in the infected mammalian cells is at the level of viral protein translation as was shown in infected avian cells. 40 However, it could still be argued that induction of the IFN gene, in response to NDV infection, is deficient in the A549 cells and thus viral replication is not blocked. To address this issue, induction of IFN-b gene upon NDV infection was directly analysed in the tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Selective oncolytic effect of an attenuated Newcastle disease virus (NDV-HUJ) in lung tumors

et al. 2008

View full text Add to dashboard Cite

Newcastle disease virus (NDV), an avian paramyxovirus, has a potential oncolytic effect that may be of significance in the treatment of a variety of cancer diseases. An attenuated lentogenic isolate of NDV (HUJ) demonstrated a selective cytopathic effect upon a panel of human and mouse lung tumor cells, as compared to human nontumorigenic lung cells. The virus-selective oncolytic effect is apoptosis dependent, and related to higher levels of viral transcription, translation and progeny virus formation. Furthermore, NDV-HUJ oncolytic activity is directed in-cis and not through induction of cytokines, that may act in-trans on neighboring cells. Development of primary lung tumors and of the consequent metastasis in mice inoculated with mouse lung tumor cells 3LL-D122 was decreased following treatment with NDV-HUJ. The preferential killing of the tumor cells is not due to a deficiency in the interferon (IFN) system, as expression of the IFN-b gene, in the infected cells, is properly induced. Moreover, pretreatment with IFN effectively protected the tumor cells from the virus oncolytic effect. We conclude therefore, that NDV-HUJ should have a significant benefit in the treatment of lung cancer as well as other malignancies.

show abstract

Newcastle Disease Virus

Miller¹,

Afonso²

2011

Encyclopedia of Life Sciences

View full text Add to dashboard Cite

Newcastle disease virus (NDV), a member of the Avulavirus genus in the Paramyxoviridae family, has a ribonucleic acid (RNA) genome that is negative sense, nonsegmented and single‐stranded. The genome codes for six structural proteins: nucleocapsid, phosphoprotein (P), matrix, fusion, hemagglutinin–neuraminidase and the RNA‐directed RNA polymerase, in addition to the nonstructural V protein that is produced by a frame shift in the P coding region. Virulent forms of NDV (vNDV) contain multiple basic amino acids in the fusion cleavage site along with a phenylalanine (F) at position 117, are found worldwide and are endemic in some countries. Infections of poultry species with vNDV lead to trade restrictions. Although all NDV strains are of one serotype, their genomes evolve over time, becoming more diverse. Strains of NDV have been used as viral vectors to formulate vaccines for other infectious diseases and experimentally to treat human cancers. The virus causes conjunctivitis in humans. Key Concepts: Virulent NDV (vNDV) is the aetiological agent of one of the most prevalent and virulent avian diseases in the world, and causes millions of birds to die, and significantly affects the poultry industries of many countries in Africa, Asia and South America. Lentogenic NDV (loNDV) is widely distributed in wild birds where it does not cause significant disease or clinical signs. Isolates of NDV are genetically diverse with at least two classes of viruses, each divided into 10 genotypes. Depending on the virulence of the NDV isolate and the immune status of the host, Newcastle disease produces a large range of clinical signs. The fusion protein cleavage site is a key determinant of virulence and a key element utilised for modern diagnostics and classification. Because all NDV isolates are of a single serotype vaccines prepared with any NDV isolate should protect against disease from any other NDV infection. Neutralising antibodies to the Fusion (F) and hemagglutinin–neuraminidase (HN) proteins of NDV are known to be important in preventing morbidity and morality from Newcastle disease. Even vaccinated birds with high antibody titre to NDV will become infected when exposed to virulent NDV and these vaccinated birds will shed virulent NDV in oral secretion and fecal matter. The genome of NDV has been used as a vaccine vector to carry foreign genes of other organisms for use in both animals and humans.

show abstract

Newcastle Disease Virus (NDV)-Based Assay Demonstrates Interferon-Antagonist Activity for the NDV V Protein and the Nipah Virus V, W, and C Proteins

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

Cited by 344 publications

References 60 publications

Identification of the Nuclear Export Signal and STAT-Binding Domains of the Nipah Virus V Protein Reveals Mechanisms Underlying Interferon Evasion

Identification of the Nuclear Export Signal and STAT-Binding Domains of the Nipah Virus V Protein Reveals Mechanisms Underlying Interferon Evasion

Selective oncolytic effect of an attenuated Newcastle disease virus (NDV-HUJ) in lung tumors

Newcastle Disease Virus

Contact Info

Product

Resources

About