Neutralizing antibody responses and evolution of antigenic variants in monozygotic twin lambs infected with phenotypically distinct ovine lentiviruses

Ovine lentivirus (OvLV) isolates 85/34 (OvlV 34) and 84/28 (OvLV 28) were i nitially characterized as phenotypically distinct "rapid/high" and "slow/lo w" strains based on replication kinetics, syncytiogenesis, and cell lysis i n vitro. In the present study, sera from OvLV-34- or OvLV-28-infected monoz ygotic twin lambs defined these virus strains as distinct neutralization se rotypes. We also show that immune recognition of at least one OvlV neutrali zation epitope is influenced by genetic differences between lambs. Addition al studies determined the neutralization phenotype of virus isolates from a lveolar macrophages of OvLV-34- or OvLV-28-infected lambs, evaluated the ro le of neutralizing antibodies in selection and persistence of antigenic var iants, and related the severity of OvLV-induced lymphoid interstitial pneum onia (LIP) to the evolution of neutralization variants. These studies demon strate that (i) macrophage-associated OvlV neutralization variants can aris e in the presence or the absence of neutralizing antibodies directed to ino culum viruses, (ii) OvlV variants persist in macrophages in the presence of serum neutralizing antibodies, and (iii) the emergence of OvlV variants is apparently unrelated to the severity of LIP. (C) 1999 Academic Press.