The nucleocapsid protein of severe acute respiratory syndrome coronavirus inhibits cell cytokinesis and proliferation by interacting with translation elongation factor 1alpha.
Severe acute respiratory syndrome coronavirus (SARS-CoV) is the etiological agent of SARS, an emerging disease characterized by atypical pneumonia. Using a yeast two-hybrid screen with the nucleocapsid (N) protein of SARS-CoV as a bait, the C terminus (amino acids 251 to 422) of the N protein was found to interact with human elongation factor 1-alpha (EF1alpha), an essential component of the translational machinery with an important role in cytokinesis, promoting the bundling of filamentous actin (F-actin). In vitro and in vivo interaction was then confirmed by immuno-coprecipitation, far-Western blotting, and surface plasmon resonance. It was demonstrated that the N protein of SARS-CoV induces aggregation of EF1alpha, inhibiting protein translation and cytokinesis by blocking F-actin bundling. Proliferation of human peripheral blood lymphocytes and other human cell lines was significantly inhibited by the infection of recombinant retrovirus expressing SARS-CoV N protein.
Zhou
Bing
B
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology, Beijing, China.
Liu
Junli
J
Wang
Qiuna
Q
Liu
Xuan
X
Li
Xiaorong
X
Li
Ping
P
Ma
Qingjun
Q
Cao
Cheng
C
D000199:Actins / Q000378:metabolism; D026481:Blotting, Far-Western; D002460:Cell Line; D049109:Cell Proliferation; D000086462:Coronavirus Nucleocapsid Proteins; D048749:Cytokinesis / Q000502:physiology*; D006801:Humans; D047468:Immunoprecipitation; D008214:Lymphocytes / Q000821:virology; D019590:Nucleocapsid Proteins / Q000378:metabolism*; D020648:Peptide Elongation Factor 1 / Q000378:metabolism*; D011485:Protein Binding; D014176:Protein Biosynthesis / Q000502:physiology*; D025941:Protein Interaction Mapping; D045473:Severe acute respiratory syndrome-related coronavirus / Q000502:physiology*; D020349:Surface Plasmon Resonance; D020798:Two-Hybrid System Techniques
D000199:Actins; D000086462:Coronavirus Nucleocapsid Proteins; D019590:Nucleocapsid Proteins; D020648:Peptide Elongation Factor 1