Blocking measles virus infection with a recombinant soluble form of, or monoclonal antibodies against, membrane cofactor protein of complement (CD46).
Human membrane cofactor protein (MCP, CD46) functions as an inhibitor of the complement (C) cascade to protect host cells from C attack, and as a receptor for measles virus (MV). Normal human sera contains 10-60 ng/ml of naturally produced soluble forms of MCP, which is also a cofactor for the factor I-mediated inactivation of C3b. We produced monoclonal antibodies (mAb) against MCP and a recombinant soluble form of MCP similar to the natural soluble forms, and tested their ability to block MV infection. Vero cells and CHO cells expressing human MCP were the targets. Of the antibodies tested, M75 and M177, which blocked the C regulatory activity of MCP, efficiently blocked MV infection. More than 50 micrograms/ml of the soluble form moderately blocked MV infection of CHO cells expressing MCP, but barely blocked that of Vero cells. The two mAb and the soluble form also inhibited MV H protein-mediated green monkey erythrocyte rosette formation. A quantitative analysis suggested that 30 micrograms/ml of the soluble form functionally corresponded to 0.2 microgram/ml of M177 or M75. These data established that the C regulatory function and the MV receptor function of MCP were blocked simultaneously by the individual mAb, and that soluble forms of MCP could inhibit MV infection in cells expressing human MCP, although doses far higher than the natural concentration of soluble MCP were required.
Seya
T
T
Department of Immunology, Center for Adult Diseases Osaka, Japan.
Kurita
M
M
Hara
T
T
Iwata
K
K
Semba
T
T
Hatanaka
M
M
Matsumoto
M
M
Yanagi
Y
Y
Ueda
S
S
Nagasawa
S
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004903:Erythrocyte Aggregation; D006801:Humans; D008457:Measles / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D012397:Rosette Formation; D012995:Solubility; D014764:Viral Proteins / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C497857:CD46 protein, human; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D014764:Viral Proteins