Herpes simplex virus which had been sensitized with immunoglobulin M antibody was neutralized by serum deficient in the fifth and sixth components of complement (C) but not by serum deficient in the fourth component C (C4). The sequential addition of the functionally purified components of C showed that the activated first component of C (C1[unk]) failed to neutralize sensitized virus. However, in the presence of an optimal concentration of C1[unk], the addition of C4 resulted in neutralization. The amount of virus neutralized was dependent upon the concentration of immunoglobulin M used to sensitize the virus and the concentration of C1[unk] and C4. The addition of the second component of C (C2) to reaction mixtures containing an optimal concentration of C1[unk] and a limiting concentration of C4 resulted in increased neutralization and the amount of virus neutralized was dependent upon the concentration of C2. The addition of the third component of C (C3) to reaction mixtures containing an optimal concentration of C1[unk] and limiting concentrations of C4 and C2 also resulted in increased neutralization and the amount of virus neutralized was dependent upon the concentration of C3.
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