The 3a Protein of SARS-coronavirus Induces Apoptosis in Vero E6 Cells.

Y Waye, Mary; W Law, Patrick; Wong, Chi-Hang; C Au, Thomas; Chuck, Chi-Pang; Kong, Siu-Kai; S Chan, Paul; To, Ka-Fai; I Lo, Anthony; W Chan, Judy; Suen, Yick-Keung; Edwin Chan, H Y; Fung, Kwok-Pui; Y Sung, Joseph; Lo, Y M; W Tsui, Stephen

An outbreak of severe acute respiratory syndrome (SARS) occurred in China and the first case emerged in mid November 2002. The etiologic agent of this disease was found to be a previously unknown coronavirus, SARS-CoV. The detailed pathology of SARS-CoV infection and the host response to the viral infection are still not known. The 3a gene encodes a non-structural viral protein which is predicted to be a transmembrane protein. In this study, we showed that the 3a protein was localized to the endoplasmic reticulum (ER) in 3a-transfected monkey kidney Vero E6 cells. In vitro experiments of chromatin condensation and DNA fragmentation suggest that the 3a protein may trigger apoptosis. Our data show that over-expression of a single SARS-CoV protein can induce apoptosis in vitro. Thus GFP-3a fusion protein could also be used as a biosensor for monitoring the cytopathic features of SARS infection, e.g. lymphopenia, in animal model systems, similar to nucleocapsid and 7a proteins.