Nucleocapsid protein of SARS-CoV activates interleukin-6 expression through cellular transcription factor NF-kappaB.
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.
Zhang
Xue
X
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, PR China.
Wu
Kailang
K
Wang
Di
D
Yue
Xin
X
Song
Degui
D
Zhu
Ying
Y
Wu
Jianguo
J
D019677:Artificial Gene Fusion; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry; D000086462:Coronavirus Nucleocapsid Proteins; D003593:Cytoplasm / Q000737:chemistry; D024202:Electrophoretic Mobility Shift Assay; D004847:Epithelial Cells / Q000821:virology; D017930:Genes, Reporter; D006801:Humans; D047468:Immunoprecipitation; D015850:Interleukin-6 / Q000235:genetics*; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D008168:Lung / Q000276:immunology* / Q000821:virology; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism*; D019590:Nucleocapsid Proteins / Q000276:immunology* / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology*; D017384:Sequence Deletion
D000086462:Coronavirus Nucleocapsid Proteins; D015850:Interleukin-6; D016328:NF-kappa B; D019590:Nucleocapsid Proteins; D008156:Luciferases