Severe acute respiratory syndrome coronavirus 3C-like protease-induced apoptosis

Lin, Cheng-Wen; Lin, Kuan-Hsun; Hsieh, Tsung-Han; Shiu, Shi-Yi; Li, Jeng-Yi

The pathogenesis of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is an important issue for the treatment and prevention of severe acute respiratory syndrome. Recently, SARS-CoV has been demonstrated to induce cell apoptosis in Vero-E6 cells. The possible role of SARS-CoV 3C-like protease (3CL(pro)) in virus-induced apoptosis is characterized in this study. Growth arrest and apoptosis via caspase-3 and caspase-9 activities were demonstrated in SARS-CoV 3CL(pro)-expressing human promonocyte cells. The fluorescence intensity of dihydrorhodamine 123 staining indicated that cellular reactive oxygen species were markedly increased in SARS-CoV 3CL(pro)-expressing cells. Moreover, in vivo signalling pathway assay indicated that 3CL(pro) increased the activation of the nuclear factor-kappa B-dependent reporter, but inhibited activator protein-1-dependent transcription. This finding is likely to be responsible for virus-induced apoptotic signalling.