Mechanism of antibody-independent activation of the first component of complement (Cl) on retrovirus membranes.

Murine leukemia viruses activate human C1 in the absence of specific antibody. Such activation requires the binding of C1 to the viral surface through two subcomponents, C1q and C1s. This conclusion is based on the following results. (1) Isolated human C1q and C1s bind the same membrane protein on virions. (2) Binding one subcomponent is independent of the other. (3) Only dimeric C1s binds, whereas monomeric C1s, prepared by dissociation with ethylenediaminetetraacetate (EDTA), has no affinity for the virus. (4) The activated C1s dimer, C1s, does not attach to the virus. (5) Saturation of C1s binding sites on the viral surface does not prevent binding of macromolecular C1, but such bound C1 is not activated. (6) No exchange occurs between C1s bound to the viral membrane and C1s contained in C1, which in turn is attached via C1q to the same virus. Therefore activation occurs only when both C1q and C1s in the same C1 complex in contact with the viral activator. Human C1r has no affinity for the virus nor does guinea pig C1s. The latter result explains why guinea pig serum does not function in antibody-independent virolysis.