Virulence of mousepox virus is independent of serpin-mediated control of cellular cytotoxicity

We have investigated whether the differential virulence seen of two Ectrome lia (Ect) strains, Ect(Moscow) and Ect(Hampstead) egg, is due to mutation o r differential regulation of their serpins (SPI), Poxvirus encoded serine p roteinase inhibitors (serpins) have been shown to interfere with cytolytic activity of leukocytes and can also determine virulence, We show that the d educed 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, i n particular, Fas-mediated target cell lysis, by allorective effecters. Vir us 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 d ata demonstrate that in Ect infection the perforin-mediated cytolytic pathw ay is not the primary target of serpins and suggest that the apparent atten uation of Ect(Hampstead) Seen in B6 mice is due to control elements distinc t from SRI-1, 2, and 3.