Abstract

Canine parvovirus (CPV) emerged in 1978 and spread worldwide, and is now a widespread endemic virus of dogs. CPV is a host range variant of the feline panleukopenia virus (FPV). Between 1979 and 1980 the original CPV strain (CPV-2) was replaced worldwide by an antigenic and host range variant (CPV-2a). The new canine host range of CPV was determined by changes within three capsid positions, and those changes also alter the antigenic structure of the capsid. The capsids bind the transferrin receptor (TfR) on feline cells, but canine cell infection requires the additional ability to bind the canine TfR. The feline and canine TfRs were expressed and purified, and distinct binding properties were seen for each receptor-capsid combination. Purified complexes of capsids with the feline TfR complexes showed only 1 to 3 TfRs bound per capsid, fewer than the 20 to 24 predicted.

Antibodies have been suggested to bind primarily to two positions on the capsid; site A on a raised region near the threefold axis of symmetry, and site B on a ridge on the side of that raised region. However, when the true binding sites of 8 different antibodies were identified by cryo-EM reconstructions of antibody Fabs with capsids those showed that the antibodies contacted >60% of the capsid surface. There is complete overlap of the receptor and many antibody binding sites, but some of those antibodies did not neutralize efficiently as Fabs. Two Fabs that did neutralize to high levels bound to antigenic site B in a particular orientation. Surprisingly, the two common regions of overlap between the groups of antibodies coincided almost exactly with the positions of known escape mutations of the viruses. As many changes in the capsids affect both antibody and TfR binding, this suggests complex selection pressures on the virus structure.