Molecular advances in the cell biology of SARS-CoV and current disease prevention strategies

Stark, Caren J; Atreya, CD

It has been shown that the SARS-CoV N protein selectively activates the Activator Protein-1 (AP-1) signal transduction pathway, which regulates a wide variety of cellular processes including cell proliferation, differentiation, and apoptosis [33] . Such viral induced modifications of the AP-1 pathway may play a significant role in the viral replicative strategy. Recently, another group demonstrated that the S protein alone induces AP-1 activation and that the region from 324-688 amino acids within the S protein is essential for AP-1 activation-dependent IL-8 induction [34] . Another SARS-CoV protein, the U122 ORF of unknown function (also known as X4), was shown to be produced in virus infected Vero E6 cells and expression of this protein alone was shown to induce apoptosis in cell culture [35, 36] . This raises the question of how apoptosis of SARS-CoV infected cells is balanced in order for the virus to survive and propagate (Figure 1 ). This has been addressed to some extent in recent studies which indicate that SARS-CoV infection of Vero E6 cells induces both pro-apoptotic [activation of p38 mitogen-activated protein kinase (MAPK)] and anti-apoptotic [activation of the protein kinase B (PKB, also known as Akt)] signaling pathways, although Akt induction appears to be insufficient to prevent the virus-induced apoptosis [37, 38] . Exactly how SARS-CoV manipulates these cellular signaling pathways to facilitate viral replication remains to be determined.