Elsevier

Virology

Volume 365, Issue 2, 1 September 2007, Pages 324-335
Virology

Nucleocapsid protein of SARS-CoV activates interleukin-6 expression through cellular transcription factor NF-κB

https://doi.org/10.1016/j.virol.2007.04.009 Get rights and content
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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-κB binding element was required for IL-6 expression regulated by N protein. Further studies demonstrated that N protein bound directly to NF-κB element on the promoter. We also showed that N protein activated IL-6 expression through NF-κB by facilitating the translocation of NF-κB 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.

Keywords

SARS-CoV
N protein
Gene regulation
Virus infection
Pathogenesis
IL-6
Inflammation
NF-κB

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