Modulation of Host Cell Death by SARS Coronavirus Proteins

Both types of cell death, namely necrosis and apoptosis, are found in organs of SARS coronavirus (CoV) infected patients. The gastrointestinal tract, however, although also a target for SARS-CoV replication, is obviously not affected by cell death mechanisms. Such differences in cell death induction are paralleled by in-vitro studies. In a colon-derived cell line (Caco-2), proapoptotic proteins were down- and antiapoptotic proteins were upregulated during SARS-CoV infection. By contrast, in SARS-CoV infected Vero E6 cells, apoptosis was induced via the p38 MAPK and caspase dependent pathways. Both apoptotic pathways, although mostly the intrinsic signal transduction, can be targeted by structural as well as accessory proteins of SARS-CoV. The fact that all structural and most of the accessory proteins of SARS-CoV are implicated in apoptotic scenarios indicates the fundamental role of apoptosis in the SARS-CoV life cycle. Interestingly, at least for the nucleocapsid protein of SARS-CoV, a cell-type specific manipulation of apoptosis was confirmed.