The virulence factor PA protein of highly pathogenic H5N1 avian influenza virus inhibits NF-κB transcription in vitro
- 329 Downloads
Nuclear factor kappa B (NF-κB) plays a crucial role in inflammation and immune responses. Our previous studies have demonstrated that the innate immune response affect H5N1 virus virulence in mice. In this study, we first showed that the PA protein of the highly pathogenic avian influenza virus strain CK10 had the strongest inhibitory effect on NF-κB activation when compared with other genes, and that it acted in a dose independent-manner. We then determined the critical amino acids of PA that contribute to this effect. Furthermore, PA also inhibited NF-κB-regulated inflammatory factors, including IL-6, IL-2, Nos-2 and TNF-α. However, the inhibitory effect on NF-κB activation mediated by PA was not associated with nuclear translocation of p65.
Compliance with ethical standards
This work was supported by the National Key Research and Development Project of China (2016YFD0501601 and 2016YFD0500202), by the National Natural Science Foundation of China (31502076), by the Special Financial Grant from the China Postdoctoral Science Foundation (2016T90515), by the Jiangsu Provincial Natural Science Foundation of China (BK20150444), by the National Key Technologies R&D Program of China (2015BAD12B01-3), 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).
Conflict of interest
The authors declare that they have no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
- 1.Dai M, McBride R, Dortmans JC, Peng W, Bakkers MJ, de Groot RJ et al (2017) Mutation of the 2nd Sialic acid-binding site resulting in reduced neuraminidase activity preceded emergence of H7N9 influenza A virus. J Virol 91(9). doi: 10.1128/JVI.00049-17
- 12.Wurzer WJ, Ehrhardt C, Pleschka S, Berberich-Siebelt F, Wolff T, Walczak H et al (2004) NF-kappaB-dependent induction of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas/FasL is crucial for efficient influenza virus propagation. J Biol Chem 279(30):30931–30937CrossRefPubMedGoogle Scholar
- 18.Sakabe S, Takano R, Nagamura-Inoue T, Yamashita N, Nidom CA, Le Quynh M et al (2013) Differences in cytokine production in human macrophages and in virulence in mice are attributable to the acidic polymerase protein of highly pathogenic influenza A virus subtype H5N1. J Infect Dis 207(2):262–271CrossRefPubMedGoogle Scholar
- 29.Zhou B, Yang Z, Feng Q, Liang X, Li J, Zanin M et al (2017) Aurantiamide acetate from baphicacanthus cusia root exhibits anti-inflammatory and anti-viral effects via inhibition of the NF-kappaB signaling pathway in influenza A virus-infected cells. J Ethnopharmacol 199:60–67CrossRefPubMedGoogle Scholar