Identification of Aleutian mink disease parvovirus capsid sequences mediating antibody-dependent enhancement of infection, virus neutralization, and immune complex formation

Aleutian mink disease parvovirus (ADV) causes a persistent infection associ ated with circulating immune complexes, immune complex disease, hypergammag lobulinemia, and high levels of antiviral antibody. Although antibody can n eutralize ADV infectivity in Crandell feline kidney cells in vitro, virus i s not cleared in,vivo, and capsid-based vaccines have proven uniformly inef fective. Antiviral antibody also enables ADV to infect macrophages, the tar get cells for persistent infection, by Fc-receptor-mediated antibody-depend ent enhancement (ADE). The antibodies involved in these unique aspects of A DV pathogenesis may have specific targets on the ADV capsid. Prominent diff erences exist between the structure of ADV and other, more-typical parvovir uses, which can be accounted for by short peptide sequences in the flexible loop regions of the capsid proteins. In order to determine whether these s hort sequences are targets for antibodies involved in ADV pathogenesis, we studied heterologous antibodies against several peptides present in the maj or capsid protein, VP2. Of these antibodies, a polyclonal rabbit antibody t o peptide VP2:428-446 was the most interesting. The anti-VP2:428-446 antibo dy aggregated virus particles into immune complexes, mediated ADE, and neut ralized virus infectivity in vitro. Thus, antibody against this short pepti de can be implicated in key facets of ADV pathogenesis. Structural modeling suggested that surface-exposed residues of VP2:428-446 are readily accessi ble for antibody binding. The observation that antibodies against a single target peptide in the ADV capsid can mediate both neutralization and ADE ma y explain the failure of capsid-based vaccines.