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Cells infected with vaccinia virus secrete several virally encoded polypeptides into the medium. One of these is the 35-kDa vaccinia virus complement-control protein (VCP) that consists of 4 CCPRs homologous to complement regulatory proteins (-chain, the segment likely to carry the binding site for C4b. Like C4b-binding protein, VCP binds to C4b, has decay-accelerating activity against C4b2a, and has cofactor activity for the factor I-mediated cleavage of C4b to C4c plus C4d. In addition, it has much weaker binding, cofactor, and decay-accelerating activities on C3b and C3bBb.