The role of complement in viral infections. III. Activation of the classical and alternative complement pathways by Sindbis virus

Sindbis virus, an enveloped alphavirus of the togavirus group, causes an acute infection in mice. Previous studies have shown that the pathogenesis of Sindbis virus infection is altered in complement-(C) depleted animals. The present studies were performed to assess the capability of and requirements for Sindbis virus to activate the C system in vitro. It was found that Sindbis virus, grown in either hamster or chicken fibroblasts, could activate C3 in a variety of sera. Sindbis virus consumed C3 in normal human serum (NHS) and EGTA-treated HS, as well as in normal guinea pig serum (GPS) and C4D-deficient GPS. These results indicated that Sindbis virus was capable of activating the alternative pathway. Further studies showed that C4 was consumed in NHS but not in EGTA-treated HS, suggesting that both C pathways could be activated by Sindbis virus. The activation of C3 by Sindbis virus was shown, by three methods, to require little if any antibody. The sera used in the above studies had no detectable antiviral antibody; Sindbis virus consumed C3 in sera from three patients with agammaglobulinemia; Sindbis virus consumed C3 in sera absorbed with the cells in which the virus was produced. It was also shown that ribonuclease A-treated virus activated C3 in normal and EGTA-treated HS, indicating that C3 activation was not due to the presence of RNA adsorbed to the surface of the virion. These results demonstrate that Sindbis virus is capable of activating the classical and alternative C pathways in the absence of detectable neutralizing antiviral antibody.