Activation of NF-κB by the Full-length Nucleocapsid Protein of the SARS Coronavirus

Abstract

The severe acute respiratory syndrome coronavirus (SARS‐CoV) is the major causative agent for the worldwide outbreak of SARS in 2003. The mechanism by which SARS‐CoV causes atypical pneumonia remains unclear. The nuclear factor kappa B (NF‐κB) is a key transcription factor that activates numerous genes involved in cellular immune response and inflammation. Many studies have shown that NF‐κB plays an important role in the pathogenesis of lung diseases. In this study, we investigated the possible regulatory interaction between the SARS‐CoV nucleocapsid (N) protein and NF‐κB by luciferase activity assay. Our results showed that the SARS‐CoV N protein can significantly activate NF‐κB only in Vero E6 cells, which are susceptible to SARS‐CoV infection, but not in Vero or HeLa cells. This suggests that NF‐κB activation is cell‐specific. Furthermore, NF‐κB activation in Vero E6 cells expressing the N protein is dose‐dependent. Further experiments showed that there is more than one function domain in the N protein responsible for NF‐κB activation. Our data indicated the possible role of the N protein in the pathogenesis of SARS.Edited by Bing SUN