The SARS coronavirus nucleocapsid protein induces actin reorganization and apoptosis in COS-1 cells in the absence of growth factors.
In March 2003, a novel coronavirus was isolated from patients exhibiting atypical pneumonia, and was subsequently proven to be the causative agent of the disease now referred to as SARS (severe acute respiratory syndrome). The complete genome of the SARS-CoV (SARS coronavirus) has since been sequenced. The SARS-CoV nucleocapsid (SARS-CoV N) protein shares little homology with other members of the coronavirus family. In the present paper, we show that SARS-CoV N is capable of inducing apoptosis of COS-1 monkey kidney cells in the absence of growth factors by down-regulating ERK (extracellular-signal-regulated kinase), up-regulating JNK (c-Jun N-terminal kinase) and p38 MAPK (mitogen-activated protein kinase) pathways, and affecting their downstream effectors. SARS-CoV N expression also down-regulated phospho-Akt and Bcl-2 levels, and activated caspases 3 and 7. However, apoptosis was independent of the p53 and Fas signalling pathways. Furthermore, activation of the p38 MAPK pathway was found to induce actin reorganization in cells devoid of growth factors. At the cytoskeletal level, SARS-CoV N down-regulated FAK (focal adhesion kinase) activity and also down-regulated fibronectin expression. This is the first report showing the ability of the N protein of SARS-CoV to induce apoptosis and actin reorganization in mammalian cells under stressed conditions.
Surjit
Milan
M
Virology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Road, New Delhi 110067, India.
Liu
Boping
B
Jameel
Shahid
S
Chow
Vincent T K
VT
Lal
Sunil K
SK
D000199:Actins / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D019556:COS Cells; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D016895:Culture Media, Serum-Free; D015536:Down-Regulation; D005353:Fibronectins / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006133:Growth Substances / Q000502:physiology; D016023:Integrins / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019590:Nucleocapsid Proteins / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D045473:Severe acute respiratory syndrome-related coronavirus / Q000502:physiology*; D014162:Transfection; D015854:Up-Regulation
D000199:Actins; D016895:Culture Media, Serum-Free; D005353:Fibronectins; D006133:Growth Substances; D016023:Integrins; D019590:Nucleocapsid Proteins; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; D051416:Focal Adhesion Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D020169:Caspases