A point mutation in the Sendai virus accessory C proteins attenuates virulence for mice, but not virus growth in cell culture

Abstract

A mutant Sendai virus (SeV(MVC)), which grows much better than its progenitor virus (SeV(M)) in cell culture, but, in strong contrast to SeV(M), is totally avirulent for mice, has been described. SeV(MVC) contains two amino acid substitutions relative to SeV(M), namely, F170S in the C protein and E2050A in the L protein. We have examined which substitutions were responsible for the above phenotypes by exchanging the C gene of our reference strain Z with those of SeV(H) (another reference strain), SeV(M), and SeV(MVC), in turn. We have found that the F170S mutation in the C(MVC) protein is responsible both for enhanced replication in cell culture and for avirulence in mice. Avirulence appeared to be due to restricted viral replication primarily after day 1, implicating some aspect of innate immunity in this process. The SeV C proteins thus appear to be required for multiple cycles of replication in mice.