Failure of neutralizing antibody to regulate CAE lentivirus expression in vivo

Sequential isolates of caprine arthritis-encephalitis lentivirus (CAEV) were obtained from clinically arthritic carpal joints of three Saanen goats between 36.4 and 44.9 months after infection with biologically cloned CAEV isolate 63. These virus isolates and the CAEV-63 inoculum were evaluated for neutralization by autologous sera. Neutralizing antibody to CAEV-63 persisted throughout the period of virus isolations. Five CAEV isolates from cell-free synovial fluid and six isolates from synovial fluid cells were neutralized by autologous sera at the time of virus isolation and up to 38.7 months prior to virus isolation. Comparison of serum neutralizing antibody titers for CAEV-63 and selected CAEV isolates demonstrated that neutralizing antibody responses were predominantly type-specific. Six virus isolates were resistant to neutralization by coincident autologous sera; however, neutralization assays using postisolation sera indicated that four of these isolates did not elicit detectable neutralizing antibody responses. Results indicate that (i) CAEV replication persists in the presence of neutralizing antibody and (ii) the neutralization phenotype of CAEV variants depends on the relative immunodominance of antigenically variable neutralization epitopes. We suggest that neutralizing antibody responses are a consequence of CAEV antigenic diversity and that variants are not selected based on resistance to neutralization. Enhancement of virus infectivity by nonneutralizing antibody is a possible mechanism of positive selection of antigenic variants.