SARS-CoV accessory protein 3b induces AP-1 transcriptional activity through activation of JNK and ERK pathways.

The outbreak of severe acute respiratory syndrome (SARS) in 2003 in China, characterized by atypical pneumonia, was associated with the emergence of a novel coronavirus named severe acute respiratory syndrome coronavirus (SARS-CoV). Eight accessory proteins of SARS coronavirus were the suspected players in the pathogenesis of the virus. Among them, protein 3b localizes to the nucleus and behaves as an interferon antagonist by inhibiting IRF3 activation. However, the effect of 3b on the activity of other common host transcription factors remains unexplored. In this work, we studied the effect of 3b on the transcriptional activity of AP-1. Our findings elucidate augmentation of AP-1-dependent gene expression in 3b-transfected Huh7 cells. Reporter gene and mobility shift assays depict an increase in the AP-1 transcriptional and DNA binding activity in the presence of 3b. This increase in activity correlates with the activation of ERK and JNK pathways. Furthermore, 3b expression potentiates AP-1-driven promoter activity of proinflammatory cytokine MCP-1, suggesting a plausible role for 3b as a virulence factor that might function by upregulating AP-1-dependent cytokine levels in SARS-CoV infection.