Analysis of antibody responses to phenotypically distinct lentiviruses.

To define the immune responses against phenotypically and pathogenically distinct lentiviruses, we used an immunoblotting assay to study antibodies to viral proteins of ovine lentivirus (OvLV) in 16 experimentally and 12 naturally infected sheep. Two distinct phenotypes of OvLV were used to experimentally infect lambs: strain 85/34, a "rapid/high" isolate which rapidly induced lysis in infected primary macrophage cultures and replicated to relatively high titers, and strains 84/28 and 85/14, "slow/low" isolates which induced slowly progressive syncytia with minimal lysis in vitro and replicated only to low titers in the same cell type. Serum antibodies against four major viral structural proteins, gp105, p25, p16, and p14, were detected. In a longitudinal study of experimentally infected lambs, the antibody to p25 (major gag protein) usually appeared first (average, about 3 weeks postinoculation [p.i.]) and was followed in about 2 weeks by p16, p14, and gp105 almost simultaneously. Six of 16 animals did not develop anti-p14 antibody by the time of necropsy at 9 to 29 weeks p.i. Two of 10 lambs which developed antibody to p14 had the antibody only transiently from 3 to 8 or 13 weeks p.i. and lost it by the time of necropsy at 21 or 22 weeks p.i. In contrast, antibodies to the other three structural proteins remained fairly constant until the time of necropsy. There were differences in the antibody responses of the experimentally infected lambs to the two phenotypes of OvLV. Seven of 10 (70%) lambs which were inoculated with the rapid/high strain developed antibody to p14, whereas only 17% of the lambs inoculated with the slow/low strains had antibody to this protein. In the longitudinal study, no decline was observed in the activity of any specific antibody such as that which occurs with anti-p24 antibody in human immunodeficiency virus infection, except in the case of anti-p14 antibody in two lambs. There were no significant differences in antibody titers against p25, p16, and p14 in final blood samples between rapid/high virus- and slow/low virus-infected groups. However, the rapid/high virus-infected group developed a fivefold-higher geometric mean titer of anti-env product (gp 105) antibody than did the slow/low virus-infected group (P </= 0.1). Antibody titers to all major structural proteins, except p14, in the naturally infected sheep were markedly lower than those in experimentally induced OvLV infections (P </= 0.01). The failure of the slow/low virus-infected group to develop anti-p14 antibody may suggest diminished viral replication in vivo or a failure of the host to recognize p14 in the slow/low virus-infected group. Since the geometric mean antibody titer to gp105 was threefold higher in lambs with lymphoid interstitial pneumonia than in those without lesions and since no differences were observed in the titers of other antiviral antibodies between these groups, we found no evidence to suggest that levels of such antibodies correlated with protection from OvLV-induced disease.