Activation of NF-kappaB by the full-length nucleocapsid protein of the SARS coronavirus.
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-kappaB) is a key transcription factor that activates numerous genes involved in cellular immune response and inflammation. Many studies have shown that NF-kappaB 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-kappaB by luciferase activity assay. Our results showed that the SARS-CoV N protein can significantly activate NF-kappaB only in Vero E6 cells, which are susceptible to SARS-CoV infection, but not in Vero or HeLa cells. This suggests that NF-kappaB activation is cell-specific. Furthermore, NF-kappaB 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-kappaB activation. Our data indicated the possible role of the N protein in the pathogenesis of SARS.
Liao
Qing-Jiao
QJ
State Key Laboratory of Virology, College of Life Science, Wuhan University, Wuhan 430072, China.
Ye
Lin-Bai
LB
Timani
Khalid Amine
KA
Zeng
Ying-Chun
YC
She
Ying-Long
YL
Ye
Li
L
Wu
Zheng-Hui
ZH
D000818:Animals; D002522:Chlorocebus aethiops; D000086462:Coronavirus Nucleocapsid Proteins; D006367:HeLa Cells; D006801:Humans; D009154:Mutation; D016328:NF-kappa B / Q000502:physiology*; D019913:Nuclear Localization Signals; D019590:Nucleocapsid Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D045473:Severe acute respiratory syndrome-related coronavirus / Q000737:chemistry* / Q000502:physiology*; D014709:Vero Cells; D014779:Virus Replication
D000086462:Coronavirus Nucleocapsid Proteins; D016328:NF-kappa B; D019913:Nuclear Localization Signals; D019590:Nucleocapsid Proteins