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The PA-interacting host protein nucleolin acts as an antiviral factor during highly pathogenic H5N1 avian influenza virus infection

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Abstract

Polymerase acidic (PA) protein is a multifunctional regulator of influenza A virus (IAV) replication and pathogenesis. In a previous study, we reported that nucleolin (NCL) is a novel PA-interacting host protein. In this study, we further explored the role of NCL during highly pathogenic H5N1 avian influenza virus infection. We found that depletion of endogenous NCL in mammalian cells by siRNA targeting during H5N1 infection resulted in significantly increased viral polymerase activity, elevated viral mRNA, cRNA and vRNA synthesis, accelerated viral replication, and enhanced apoptosis and necrosis. Moreover, siRNA silencing of NCL significantly exacerbated the inflammatory response, resulting in increased secretion of IL-6, TNF-α, TNF-β, CCL-4, CCL-8, IFN-α, IFN-β and IFN-γ. Conversely, overexpression of NCL significantly decreased IAV replication. Collectively, these data show that NCL acts as a novel potential antiviral factor during H5N1 infection. Further studies exploring the antiviral mechanisms of NCL may accelerate the development of new anti-influenza drugs.

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Funding

This work was supported by the National Natural Science Foundation of China (31502076), by the Jiangsu Provincial Natural Science Foundation of China (BK20150444), by the Special Financial Grant from the China Postdoctoral Science Foundation (2016T90515), by the National Key Research and Development Project of China (2016YFD0501601 and 2016YFD0500202), by the National Key Technologies R&D Program of China (2015BAD12B01-3), by the Postdoctoral Science Foundation of Jiangsu Province, China (1501015B), by the Natural Science Foundation of the Higher Education Institutions of Jiangsu Province, China (15KJB230006), by the Earmarked Fund for Modern Agro-Industry Technology Research System (nycytx-41-G07), and by A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

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  1. Zhao Gao and Jiao Hu contributed equally to this work.

Authors and Affiliations

  1. Animal Infectious Disease Laboratory, School of Veterinary Medicine, College of Veterinary Medicine, Yangzhou University, 48 East Wenhui Road, Yangzhou, 225009, Jiangsu, China

    Zhao Gao, Jiao Hu, Xiaoquan Wang, Qian Yang, Yanyan Liang, Chunxi Ma, Dong Liu, Kaituo Liu, Xiaoli Hao, Min Gu, Xiaowen Liu & Xiufan Liu

  2. Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, Jiangsu, China

    Zhao Gao, Jiao Hu, Xiaoquan Wang, Qian Yang, Yanyan Liang, Chunxi Ma, Dong Liu, Kaituo Liu, Xiaoli Hao, Min Gu, Xiaowen Liu, Xin-an Jiao & Xiufan Liu

  3. Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, China

    Xin-an Jiao

  4. Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-food Safety and Quality, Ministry of Agriculture of China (26116120), Yangzhou University, Yangzhou, China

    Zhao Gao, Jiao Hu, Xiaoquan Wang, Qian Yang, Yanyan Liang, Chunxi Ma, Dong Liu, Kaituo Liu, Xiaoli Hao, Min Gu, Xiaowen Liu, Xin-an Jiao & Xiufan Liu

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  1. Zhao Gao
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  2. Jiao Hu
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  10. Min Gu
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Correspondence to Xiufan Liu.

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Gao, Z., Hu, J., Wang, X. et al. The PA-interacting host protein nucleolin acts as an antiviral factor during highly pathogenic H5N1 avian influenza virus infection. Arch Virol 163, 2775–2786 (2018). https://doi.org/10.1007/s00705-018-3926-3

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