Viral modulation of cell death by inhibition of caspases

Caspases are key effectors of the apoptotic process. Some of them play important roles in the immune system, being involved in the proteolytic maturation of the key cytokines, including interleukin 1beta (IL-1beta) and IL-18. The latter directs the production of interferon gamma (IFN-gamma). Among pathogens, particularly viruses express various modulators of caspases that inhibit their activity by direct binding. By evading the apoptotic process, viruses can better control their production in the infected cell and avoid the attack of the immune system. Targeting the maturation of the key cytokines involved in the initiation of (antiviral) immune response helps to avoid recognition and eradication by the immune system. The three main classes of caspase inhibitors frequently found among viruses include serine proteinase inhibitors (serpins: CrmA/SPI-2), viral IAPs (vIAPs) and p35. Their molecular mechanisms of action, structures and overall influence on cellular physiology are discussed in the review below.