Virulence of Mousepox Virus Is Independent of Serpin-Mediated Control of Cellular Cytotoxicity

Abstract

We have investigated whether the differential virulence seen of two Ectromelia (Ect) strains, Ect_Moscow and Ect_Hampstead egg, is due to mutation or differential regulation of their serpins (SPI). Poxvirus encoded serine proteinase inhibitors (serpins) have been shown to interfere with cytolytic activity of leukocytes and can also determine virulence. We show that the deduced amino acid sequences of SPI-1, 2, and 3 are identical for the highly virulent Ect_Moscow and the low virulent Ect_Hampstead strains and that the two viruses express similar potential to inhibit T-cell cytotoxicity, in particular, Fas-mediated target cell lysis, by allorective effectors. Virus titres in wild type B6 mice were effectively controlled very early after inoculation with Ect_Hampstead as compared with Ect_Moscow, but lack of perforin renders B6 mice similarly susceptible to both virus strains. The data demonstrate that in Ect infection the perforin-mediated cytolytic pathway is not the primary target of serpins and suggest that the apparent attenuation of Ect_Hampstead seen in B6 mice is due to control elements distinct from SPI-1, 2, and 3.