Smallpox repays the complement

Smallpox was eradicated in 1977 following a prolonged worldwide vaccination effort, but in the light of recent suspected bioterrorist acts understanding the molecular mechanism of this infection remains critically important. In May 28 Proceedings of the National Academy of Sciences, Ariella Rosengard and colleagues from University of Pennsylvania School of Medicine, Philadelphia show that variola overcomes the human immune response by expressing a highly efficient inhibitor of human complement (Proc Natl Acad Sci USA 2002, 10.1073/pnas.112220499).

Authentic variola proteins are not available for research so Rosengard et al. engineered the smallpox inhibitor of complement enzymes (SPICE) — a homologue of the vaccinia virulence factor, vaccinia virus complement control protein (VCP). When they compared VCP and SPICE and they found that SPICE was nearly 100-fold more potent than VCP at inactivating human C3b and 6-fold more potent at inactivating C4b. SPICE was also more human complement-specific than VCP and may explain ...