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Published on: January 12, 2020
Nucleocapsid protein of SARS-CoV activates interleukin-6 expression through cellular transcription factor NF-kappaB
Xue Zhang1, Kailang Wu, Di Wang
1State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, PR China.
Abstract:
High levels of interleukin-6 (IL-6) in the acute stage associated with lung lesions were found in SARS patients. To evaluate the mechanisms behind this event, we investigated the roles of SARS-CoV proteins in the regulation of IL-6. Results showed that the viral nucleocapsid (N) protein activated IL-6 expression in a concentration-dependent manner. Promoter analyses suggested that NF-kappaB binding element was required for IL-6 expression regulated by N protein. Further studies demonstrated that N protein bound directly to NF-kappaB element on the promoter. We also showed that N protein activated IL-6 expression through NF-kappaB by facilitating the translocation of NF-kappaB from cytosol to nucleus. Mutational analyses revealed that two regions of N protein were essential for its function in the activation of IL-6. These results provided new insights into understanding the mechanism involved in the function of SARS-CoV N protein and pathogenesis of the virus.
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