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Toll-like receptor 3 inhibits Newcastle disease virus replication through activation of pro-inflammatory cytokines and the type-1 interferon pathway

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Abstract

Newcastle disease virus (NDV) is an avian paramyxovirus that can selectively replicate in and destroy human tumor cells. In this report, we demonstrate that NDV infection in HeLa cells leads to the activation of the pattern recognition Toll-like receptor 3 (TLR3). Overexpression of TLR3 enhanced the activity of the IFN-β promoter and the transcription factor NF-kappa B (NF-κB), thereby decreasing viral protein synthesis and the virus titer. In addition, the reduction of endogenous TLR3 by small interfering RNA (siRNA) increased NDV replication. Similar anti-NDV effects were observed in DF-1 chicken fibroblast cells with the exogenous expression of chicken TLR3 (cTLR3). Immunofluorescence staining of HeLa cells indicated that the dsRNA generated during NDV replication colocalized with TLR3 in punctate subcellular structures. Altogether, our results strongly suggest that TLR3 actively participates in the recognition of the innate pro-inflammatory response after NDV infection and leads to the consequent antiviral cytokine/interferon secretion.

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Acknowledgments

We are grateful to Professor Takashi Fujita (Kyoto University, Japan) for providing the p125-luc plasmid. This work was financially supported by the Chinese National High-Tech R&D Program (2011AA10A209), the Priority Academic Program Development of Jiangsu Higher Education Institutions, the China Agriculture Research System (CARS-41-K08), and the Chinese Special Fund for Agro-Scientific Research in the Public Interest (201003012 and 201303033).

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Authors and Affiliations

  1. Jiangsu Co-Innovation Center for Prevention and Control of Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, 12 East Wenhui Road, Yangzhou, 225009, Jiangsu, People’s Republic of China

    Jinghua Cheng, Xiaorong Zhang, Song Gao & Yantao Wu

  2. Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 518 Ziyue Road, Shanghai, 200241, People’s Republic of China

    Jinghua Cheng, Yingjie Sun, Shilei Zhang, Shengqing Yu, Xusheng Qiu, Lei Tan, Cuiping Song & Chan Ding

  3. College of Veterinary Medicine, Nanjing Agriculture University, Nanjing, 210095, Jiangsu, People’s Republic of China

    Fanqing Zhang

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  1. Jinghua Cheng
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Correspondence to Yantao Wu or Chan Ding.

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Cheng, J., Sun, Y., Zhang, X. et al. Toll-like receptor 3 inhibits Newcastle disease virus replication through activation of pro-inflammatory cytokines and the type-1 interferon pathway. Arch Virol 159, 2937–2948 (2014). https://doi.org/10.1007/s00705-014-2148-6

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  • DOI: https://doi.org/10.1007/s00705-014-2148-6

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