The recognition of parvovirus capsids by antibodies

Abstract

The parvoviruses are small, non-enveloped icosahedral viruses which infect many animals, including vertebrates and arthropods. Vertebrate parvoviruses can be classified into the autonomous and the adeno-associated viruses — the autonomous parvoviruses have been examined in detail for antigenic structure. The protective immunity against parvoviruses in animals appears to be primarily antibody-mediated. The capsid of the autonomous parvoviruses is assembled from two proteins, VP1 and VP2, which overlap in sequence, with VP1 having additional N-terminal residues. Empty capsids can be assembled from VP2 alone. The structures of canine parvovirus (CPV) and feline panleukopenia virus (FPV) have been solved to better than 3·5 Å resolution, and the structure of human parvovirus, B19, has been solved to 8 Å resolution. In each case the T = 1 icosahedron is made up to 60 copies of a structural motif common to VP1 and VP2, consisting of an eight-stranded anti-parallel β-barrel. The surface of the capsid is made up primarily of large elaborate loops which connect the β-strands that make up the barrel. Antigenic epitopes have been mapped utilizing escape mutants, natural variants, peptide analysis and by expression of viral proteins. In CPV two major antigenic determinants were defined by escape mutant analysis, while peptide analysis revealed antigenic determinants in many different regions of the capsid protein, including the amino terminus of VP2. Neutralizing epitopes of B19 were found by peptide analysis in the VP1-unique region and in sequences common to VP1 and VP2. Other antigenic, but non-neutralizing, epitopes were found in the VP1–VP2 junction, as well as various other parts of the VP2 protein. The binding of a Fab derived from one neutralizing anti-CPV Mab has been examined by cryo-electron microscopy image reconstruction, which showed that 60 copies of the Fab were bound per virion. The Fab footprint covered approximately 796 Å 2of the capsid surface, in a region where escape mutations to that Mab had been previously shown to cluster. The mechanism of neutralization was not clear, but could involve interference with cell attachment, cell entry or uncoating during the process of cell infection.