Abstract
Newcastle disease virus (NDV) V protein is considered as an effector for IFN antagonism, however, the mechanism remains unknown. In this study, the expression of STAT1 and phospho-STAT1 in cells infected with NDV or transfected with V protein-expressing plasmids were analyzed. Our results showed that NDV V protein targets phospho-STAT1 reduction in the cells depends on the stimulation of IFN-α. In addition, a V-deficient genotype VII recombinant NDV strain rZJ1-VS was constructed using reverse genetic technique to confirm the results. The rZJ1-VS lost the ability to reduce phospho-STAT1 and induced higher expression of IFN-responsive genes in infected cells. Furthermore, treatment with an ubiquitin E1 inhibitor PYR-41 demonstrated that phospho-STAT1 reduction was caused by degradation, but not de-phosphorylation. We conclude that NDV V protein targets phospho-STAT1 degradation to block IFN-α signaling, which adds novel knowledge to the strategies used by paramyxoviruses to evade IFN.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Line
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Chickens
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Chlorocebus aethiops
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Genes, Viral
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Humans
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Interferon-alpha / antagonists & inhibitors*
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Interferon-alpha / metabolism
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Mice
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Mice, Inbred BALB C
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Newcastle disease virus / genetics
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Newcastle disease virus / pathogenicity*
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Newcastle disease virus / physiology*
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Phosphorylation
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Protein Structure, Tertiary
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Proteolysis
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Recombination, Genetic
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STAT1 Transcription Factor / metabolism*
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Signal Transduction
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Vero Cells
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Viral Proteins / chemistry
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Viral Proteins / genetics
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Viral Proteins / physiology*
Substances
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36 kDa V protein, Newcastle disease virus
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Interferon-alpha
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STAT1 Transcription Factor
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Viral Proteins
Grants and funding
This work was funded by (1) the Chinese National High-tech R&D Program (863 Program, 2011AA10A209),
http://program.most.gov.cn/, the funder played a role in study design and data collection and analysis. (2) National Natural Science Foundation of China (31101822),
http://www.nsfc.gov.cn/, the funder played a role in study design and data collection and analysis. (3) Chinese Special Fund for Agro-scientific Research in the Public Interest (201303033),
http://www.moa.gov.cn/, the funder played a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.