Characterization of the ectromelia virus serpin, SPI-2

Poxviruses encode multiple proteins that enable them to evade host response s. Among these are serine protease inhibitors (serpins), One of the earlies t serpins described, cowpox virus crmA, acts to inhibit inflammation and ap optosis, crmA homologous serpins, known as SPI-2, are conserved in rabbitpo x, vaccinia and variola viruses. Here, we describe the characterization of ectromelia virus (EV) SPI-2, EV SPI-2 encodes a protein of approximately 38 kDa showing >94% identity with other poxviral homologues. Conservative cha nges in amino acid sequence were found within the reactive site loop and th e serpin backbone,. Like crmA, transient expression of SPI-2 protected cell s from tumour necrosis factor-mediated apoptosis and inhibited the activity of caspases-1 and -8 but not caspases-3, -6 or granzyme B. Overall, this s tudy demonstrates that EV SPI-2 is functionally similar to crmA, based on i n vitro assays.