Conservation in vivo of protease cleavage sites in antigenic sites of poliovirus.

Polioviruses possess three major antigenic sites which have been located chemically and structurally on the particle. One of these sites, designated site 1, is strongly immunodominant for serotype 3, but highly immunorecessive for type 1. We report that monoclonal antibodies directed against site 1 of type 1 poliovirus may be isolated by an altered route of immunization of the donor mice. Site 1 is shown to be highly variable for type 1, but highly conserved for type 3 poliovirus, although the converse would be predicted from their immunodominance. The evidence presented suggests that the antigenic conservation is associated with a strong selective pressure for a proteolytic cleavage site within site 1 of type 3. As proteolytic cleavage results in the loss of the antigenicity of site 1 the presence of the cleavage site in a virus replicating in the gut in the presence of proteases would protect the virus from neutralizing antibodies directed against uncleaved site 1. The conservation of the site in type 3 is thus consistent with the view that site 1 is a significant target of a human as well as a murine immune response against type 3.