THE COWPOX VIRUS-ENCODED HOMOLOG OF THE VACCINIA VIRUS COMPLEMENT CONTROL PROTEIN IS AN INFLAMMATION MODULATORY PROTEIN

Vaccinia virus complement control protein (VCP) is encoded by vaccinia virus, with its homolog encoded by other pathogenic poxviruses includ ing variola virus. Since rodents are the primary reservoir hosts of co wpox virus (CPV) and since CPV encodes a highly conserved functional h omolog of VCP, termed here the inflammation modulatory protein (IMP), the effects of injection of CPV into the footpads of mice was determin ed in order to study the precise in vivo effects of IMP. Macroscopic e xamination of the site of injection with a recombinant virus lacking I MP (CPV-IMP) showed greater tissue damage, with more hemorrhage and in duration, than sites injected with the wild-type cowpox virus. In addi tion, the measurement of the specific swelling response carried out fo r several weeks revealed significantly greater swelling in mice inject ed with CPV-IMP. Thus, IMP modulates the complement-activated inflamma tory response in vivo. Furthermore, the diminished destruction of host tissue observed in the presence of IMP indicates symbiosis in which t he virus ensures the preservation of surrounding host tissue, possibly to support the growth of its progeny. (C) 1997 Academic Press.