Skip to main content
PMC home page
Wiley - PMC COVID-19 Collection logoLink to Wiley - PMC COVID-19 Collection
. 2005 Sep 27;37(9):607–612. doi: 10.1111/j.1745-7270.2005.00082.x

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

Qing‐Jiao LIAO 1,#, Lin‐Bai YE 1,✉, Khalid Amine TIMANI 1,#, Ying‐Chun ZENG 1, Ying‐Long SHE 1, Li YE 1, Zheng‐Hui WU 1
PMCID: PMC7109668  PMID: 16143815

Abstract

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

Keywords: severe acute respiratory syndrome coronavirus (SARS‐CoV), nucleocapsid protein, NF‐κB

References

  • 1. Drosten C, Gunther S, Preiser W, van der Werf S, Brodt HR, Becker S, Rabenau H et al. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N Engl J Med 2003, 348: 1967–1976. [DOI] [PubMed] [Google Scholar]
  • 2. Ksiazek TG, Erdman D, Goldsmith CS, Zaki SR, Peret T, Emery S, Tong S et al. Anovel coronavirus associated with severe acute respiratory syndrome. N Engl J Med 2003, 348: 1953–1966. [DOI] [PubMed] [Google Scholar]
  • 3. Rota PA, Oberste MS, Monroe SS, Nix WA, Campagnoli R, Icenogle JP, Penaranda S et al. Characterization of a novel coronavirus associated with severe acute respiratory syndrome. Science 2003, 300: 1394–1399. [DOI] [PubMed] [Google Scholar]
  • 4. Marra MA, Jones SJ, Astell CR, Holt RA, Brooks‐Wilson A, Butterfield YS, Khattra J et al. The genome sequence of the SARS‐associated coronavirus. Science 2003, 300: 1399–1404. [DOI] [PubMed] [Google Scholar]
  • 5. He R, Leeson A, Andonov A, Li Y, Bastien N, Cao J, Osiowy C et al. Activation of AP‐1 signal transduction pathway by S ARS coronavirus nucleo‐capsid protein. Biochem Biophys Res Commun 2003, 311: 870–876. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6. Surjit M, Liu B, Jameel S, Chow VT, Lal SK. The SARS coronavirus nucleocapsid protein induces actin reorganization and apoptosis in COS‐1 cells in the absence of growth factors. Biochem J 2004, 383: 13–18. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7. Li Q, Verma IM. NF‐κB regulation in the immune system. Nat Rev Immunol 2002, 2: 725–734. [DOI] [PubMed] [Google Scholar]
  • 8. Christman JW, Sadikot RT, Blackwell TS. The role of nuclear factor‐κB in pulmonary diseases. Chest 2000, 117: 1482–1487. [DOI] [PubMed] [Google Scholar]
  • 9. Peiris JS, Yuen KY, Osterhaus AD, Stohr K. The severe acute respiratory syndrome. N Engl J Med 2003, 349: 2431–2441. [DOI] [PubMed] [Google Scholar]
  • 10. Timani KA, Ye L, Ye L, Zhu Y, Wu Z, Gong Z. Cloning, sequencing, expression, and purification of SARS‐associated coronavirus nucleocapsid protein for serodiagnosis of SARS. J Clin Virol 2004, 30: 309–312. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11. Ying W, Hao Y, Zhang Y, Peng W, Qin E, Cai Y, Wei K et al. Proteomic analysis on structural proteins of severe acute respiratory syndrome coronavirus. Proteomics 2004, 4: 492–504. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12. Hicks GR, Raikhel NV. Protein import into the nucleus: An integrated view. Annu Rev Cell Dev Biol 1995, 11: 155–188. [DOI] [PubMed] [Google Scholar]
  • 13. Karin M, Cao Y, Greten FR, Li ZW. NF‐κB in cancer:From innocent bystander to major culprit. Nat Rev Cancer 2002, 2: 301–310. [DOI] [PubMed] [Google Scholar]
  • 14. Bonizzi G, Karin M. The two NF‐κB activation pathways and their role in innate and adaptive immunity. Trends Immunol 2004, 25: 280–288. [DOI] [PubMed] [Google Scholar]
  • 15. Bour S, Perrin C, Akari H, Strebel K. The human immunodeficiency virus type 1 Vpu protein inhibits NF‐κB activation by interfering with βTrCP‐mediated degradation of IκB. J Biol Chem 2001, 276: 15920–15928. [DOI] [PubMed] [Google Scholar]
  • 16. O'Mahony AM, Montano M, van Beneden K, Chen LF, Greene WC. Human T‐cell lymphotropic virus type 1 tax induction of biologically active NF‐κB requires IκB kinase‐1‐mediated phosphorylation of RelA/p65. J Biol Chem 2004. 279: 18137–18145. [DOI] [PubMed] [Google Scholar]
  • 17. Goodkin ML, Ting AT, Blaho JA. NF‐κB is required for apoptosis prevention during herpes simplex virus type 1 infection. J Virol 2003, 77: 7261–7280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18. Watashi K, Hijikata M, Marusawa H, Doi T, Shimotohno K. Cytoplasmic localization is important for transcription factor nuclear factor‐κB activation by hepatitis C virus core protein through its amino terminal region. Virology 2001, 286: 391–402. [DOI] [PubMed] [Google Scholar]
  • 19. Luftig M, Yasui T, Soni V, Kang MS, Jacobson N, Cahir‐McFarland E, Seed B et al. Epstein‐Barr virus latent infection membrane protein 1 TRAF‐binding site induces NIK/IKKα‐dependent noncanonical NF‐κB activation. Proc Natl Acad Sci USA 2004, 101: 141–146. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20. Mastronarde JG, He B, Monick MM, Mukaida N, Matsushima K, Hunninghake GW. Induction of interleukin (IL)‐8 gene expression by respiratory syncytial virus involves activation of nuclear factor (NF)‐κB and NF‐IL‐6. J Infect Dis 1996, 174: 262–267. [DOI] [PubMed] [Google Scholar]
  • 21. Simeonova PP, Luster MI. Asbestos induction of nuclear transcription factors and interleukin 8 gene regulation. Am J Respir Cell Mol Biol 1996, 15: 787–795. [DOI] [PubMed] [Google Scholar]
  • 22. DiMango E, Ratner AJ, Bryan R, Tabibi S, Prince A. Activation of NF‐κB by adherent Pseudomonas aeruginosa in normal and cystic fibrosis respiratory epithelial cells. J Clin Invest 1998, 101: 2598–2605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23. Schwartz MD, Moore EE, Moore FA, Shenkar R, Moine P, Haenel JB, Abraham E. Nuclear factor‐kappaB is activated in alveolar macrophages from patients with acute respiratory distress syndrome. Crit Care Med 1996, 24: 1285–1292. [DOI] [PubMed] [Google Scholar]
  • 24. Hart LA, Krishnan VL, Adcock IM, Barnes PJ, Chung KF. Activation and localization of transcription factor, nuclear factor‐κB, in asthma. Am J Respir Crit Care Med 1998, 158: 1585–1592. [DOI] [PubMed] [Google Scholar]
  • 25. Chang YJ, Liu CY, Chiang BL, Chao YC, Chen CC. Induction of IL‐8 release in lung cells via activator protein‐1 by recombinant baculovirus displaying severe acute respiratory syndrome‐coronavirus spike proteins: Identification of two functional regions. J Immunol 2004, 173: 7602–7614. [DOI] [PubMed] [Google Scholar]
  • 26. Lee CH, Chen RF, Liu JW, Yeh WT, Chang JC, Liu PM, Eng HL et al. Altered p3 8 mitogen‐activated protein kinase expression in different leukocytes with increment of immunosuppressive mediators in patients with severe acute respiratory syndrome. J Immunol 2004, 172: 7841–7847. [DOI] [PubMed] [Google Scholar]
  • 27. Wang T, Wang Y, Wu MC, Guan XY, Yin ZF. Activating mechanism of transcriptor NF‐kappaB regulated by hepatitis B virus X protein in hepato‐cellular carcinoma. World J Gastroenterol 2004, 10: 356–360. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Acta Biochimica et Biophysica Sinica are provided here courtesy of Wiley

RESOURCES