Activation of the alternative complement pathway by enveloped viruses containing limited amounts of sialic acid

We have demonstrated that purified enveloped viruses grown in MDBK cells, such as influenza virus, Simian virus 5 (SV5), and vesicular stomatitis virus (VSV) grown in the presence of SV5 activate the alternative complement pathway, whereas VSV grown in BHK21-F or HKCC cells and Sindbis virus grown in BHK21-F cells do not. A direct correlation between the amount of sialic acid associated with the viral surface and its ability to activate the alternative complement pathway has been demonstrated. Our results indicate that enveloped viruses that lack sialic acid are efficient activators of the alternative complement pathway, whereas those with ≥10 μg of sialic acid/mg of protein do not. Enveloped viruses with 5–10 μg of sialic acid/mg of protein are intermediate in their ability to activate the alternative complement pathway. The results of our experiments employing different enveloped viruses with biologically derived sialic acid content support the hypothesis (D. T. Fearon, 1978, Proc. Nat. Acad. Sci. USA75 1971–1975) that sialic acid is a key membrane constituent for modulating activation of C3 via the alternative complement pathway.