M and N proteins of SARS coronavirus induce apoptosis in HPF cells


Background: SARS-associated coronavirus (SARS-CoV) induced cell apoptosis and its structural proteins may play a role in this process. Objectives: To determine whether the structural proteins M and N of SARS-CoV induce apoptosis. Study design: We investigated human pulmonary fibroblast (HPF) cells, were transfected with plasmids containing the M or N gene, by TdT-mediated dUTP nick end labeling (TUNEL), Hoechst 33342 staining for nuclei, and observation of morphology. Results: We found that in the absence of serum about 16.34% of cells transfected by pcDNA3.1-M and 21.72% of N-transfected cells showed typical apoptotic characteristics, significantly different from mock-transfected cells (only 6.23%, p<0.01). Furthermore, the cells that were co-transfected with M and N proteins showed more obvious phenomena of cell death (about 36.03%). There was a statistical significance between M-transfected cells and co-transfected cells (p<0.01), and a remarkable difference between N-transfected cells and co-transfected cells (p<0.01). Conclusions: The results show that M and N proteins of SARS-CoV can induce apoptosis of HPF cells. Co-transfection of M and N enhances the induction of apoptosis by M or N alone, which also suggests that the structural proteins of SARS-CoV may play an important role not only in the process of invasion but also in the pathogenetic process in cells.



human pulmonary fibroblast


severe acute respiratory syndrome


SARS-associated coronavirus


TdT-mediated dUTP nick end labeling


  1. Chow KY, Yeung YS, Hon CC, Zeng F, Law KM, Leung FC. Adenovirus-mediated expression of the C-terminal domain of SARS-CoV spike protein is sufficient to induce apoptosis in Vero E6 cells. FEBS Lett. 2005;579(30):6699–704.

  2. Gao Hong, Peng Jingpian, Deng Wei, et al. Infection of SARS-CoV on juvenile and adult Brandt's vole Microtus brandtii. Chinese Science Bulletin. 2005;50(12):1199–204.

  3. He R, Leeson A, Ballantine M, et al. Characterization of protein– protein interactions between the nucleocapsid protein and membrane protein of the SARS coronavirus. Virus Res. 2004;105(2):121–5.

  4. Jiang Z, Zhang Y, Chen XQ, et al. Apoptosis and activation of Erk1/2 and Akt in astrocytes postischemia. Neurochem Res. 2003;28(6):831–7.

  5. Jin Rong-Hua, Zhang Yong-Hong, Ren Yi, et al. Apoptosis related proteins expression of T lymphocyte in SARS convalescent patients. Chinese J Immunol. 2004;20(2):97–9.

  6. Law PT, Wong CH, Au TC, et al. The 3a protein of severe acute respiratory syndrome-associated coronavirus induces apoptosis in Vero E6 cells. J Gen Virol. 2005;86(Pt 7):1921–30.

  7. Marra MA, Jones SJ, Astell CR, et al. The genome sequence of the SARS-associated coronavirus. Science. 2003;300(5624):1399–404.

  8. Rota PA, Oberste MS, Monroe SS, et al. Characterization of a novel coronavirus associated with severe acute respiratory syndrome. Science. 2003;300(5624):1394–9.

  9. Shi SQ, Peng JP, Li YC, et al. The expression of membrane protein augments the specific responses induced by SARS-CoV nucleocapsid DNA immunization. Mol Immunol. 2006;43(11):1791–8.

  10. 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(Pt 1):13–8.

  11. Tan YJ, Fielding BC, Goh PY, et al. Overexpression of 7a, a protein specifically encoded by the severe acute respiratory syndrome coronavirus, induces apoptosis via a caspase-dependent pathway. J Virol. 2004;78(24):14043–7.

  12. Yan H, Xiao G, Zhang J, et al. SARS coronavirus induces apoptosis in Vero E6 cells. J Med Virol. 2004;73(3):323–31.

  13. Yang Y, Xiong Z, Zhang S, et al. Bcl-xL inhibits T-cell apoptosis induced by expression of SARS coronavirus E protein in the absence of growth factors. Biochem J. 2005;392(Pt 1):135–43.

  14. Yuan X, Shan Y, Zhao Z, Chen J, Cong Y. G0/G1 arrest and apoptosis induced by SARS-CoV 3b protein in transfected cells. Virol J. 2005;2:66.

Download references

Author information

Correspondence to Jing-Pian Peng.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Zhao, G., Shi, S., Yang, Y. et al. M and N proteins of SARS coronavirus induce apoptosis in HPF cells. Cell Biol Toxicol 22, 313–322 (2006).

Download citation


  • apoptosis
  • human pulmonary fibroblasts
  • SARS-CoV