Regulation of complement activity by vaccinia virus complement-control protein.
A major protein secreted by vaccinia virus-infected cells has structural similarity to the super-family of complement-control proteins. This vaccinia complement-control protein (VCP) was studied to determine how it regulates complement activation. VCP was bound by C4b and C3b and served as a cofactor with factor I in cleaving these two molecules. VCP inhibited the formation and accelerated the decay of the classical C3 convertase. It also accelerated decay of the alternative pathway convertase, although higher concentrations were apparently needed. In vitro, therefore, VCP interfered with the classical and alternative complement pathways at several steps. In vivo, this interference may increase the virulence of vaccinia virus by enabling it to escape attack by the host's complement system.
McKenzie
R
R
Laboratory of Clinical Investigation, NIAID, National Institutes of Health, Bethesda, MD 20892.
Kotwal
G J
GJ
Moss
B
B
Hammer
C H
CH
Frank
M M
MM
D003167:Complement Activation / Q000502:physiology*; D003176:Complement C3 / Q000502:physiology*; D050577:Complement C3-C5 Convertases / Q000037:antagonists & inhibitors; D003179:Complement C3b / Q000378:metabolism; D003181:Complement C4 / Q000502:physiology*; D015935:Complement C4b / Q000378:metabolism; D003169:Complement Inactivator Proteins / Q000502:physiology*; D003170:Complement Pathway, Alternative; D003171:Complement Pathway, Classical; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D014616:Vaccinia virus / Q000472:pathogenicity*; D014764:Viral Proteins / Q000502:physiology*; D014774:Virulence
D003176:Complement C3; D003181:Complement C4; D003169:Complement Inactivator Proteins; D014764:Viral Proteins; C066459:complement-control protein, Vaccinia virus; D003179:Complement C3b; D015935:Complement C4b; D050577:Complement C3-C5 Convertases