Neutralization of vesicular stomatitis virus (VSV) by human complement requires a natural IgM antibody present in human serum.
Neutralization of VSV by human serum ws previously shown to involve C1, C2, C3, and C4 of the classical complement (C) pathway. All normal human sera tested were equivalently active in this regard. However, purified C1, C2, C3, and C4 were unable to mediate VSV neutralization. In the present studies an additional factor required for C-mediated neutralization was isolated from normal human serum and identified as a natural IgM antibody specific for a viral encoded antigen. Purified IgM bound to the virus and formed a complex that activated component C1. Normal serum concentrations of purified IgM, C1, C2, C3, C4 neutralized VSV to the same extent as normal serum. Purified IgM did not neutralize VSV alone or in conjunction with C1, C2, and C4. Inclusion of C3 resulted in full neutralization and C3b binding to the virus was demonstrated. Thus, normal human serum contains a natural antibody of the IgM class that is directed toward a viral antigen. The antibody facilitates neutralization by forming an immune complex that activates C1 and thus efficiently initiates the classical pathway at the viral surface. Neutralization occurs with C3b deposition on the viral envelope and probably results from a blanket of C protein that interferes with viral attachment to susceptible cells.
D000042:Absorption; D001666:Binding Sites, Antibody; D002460:Cell Line; D003167:Complement Activation; D003172:Complement C1; D003175:Complement C2; D003176:Complement C3; D003181:Complement C4; D006358:Hot Temperature; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology*; D046911:Macromolecular Substances; D009500:Neutralization Tests; D013280:Stomatitis / Q000276:immunology; D014721:Vesicular stomatitis Indiana virus / Q000254:growth & development / Q000276:immunology*; D014777:Virus Diseases / Q000276:immunology
D003172:Complement C1; D003175:Complement C2; D003176:Complement C3; D003181:Complement C4; D007075:Immunoglobulin M; D046911:Macromolecular Substances