Lentivirus-induced lymphoproliferative disease. Comparative pathogenicity of phenotypically distinct ovine lentivirus strains

Abstract

For investigation of the pathogenicity of lentivirus strains, which have distinctly different cytopathic phenotypes in synovial membrane cell culture, plaque-purified, lytic, and nonlytic ovine lentivirus (OvLV) isolates were inoculated intratracheally into two groups of neonatal lambs. Twelve lambs were inoculated with a lytic OvLV isolate and 3 lambs each with two nonlytic OvLV isolates. Five control lambs were inoculated with either virus-free medium or were left uninoculated. In 8 of 12 lambs inoculated with a lytic OvLV isolate mild to severe lesions of lymphoid interstitial pneumonia (LIP) and pulmonary lymphoid hyperplasia developed, 6 of 12 lambs had lesions of pulmonary lymph node follicular hyperplasia, 3 of 9 female lambs had lesions of lymphoproliferative mastitis, 3 of 10 lambs had lesions of lymphocytic/plasmacytic synovitis, and 3 lambs had no lesions. In 3 of 6 lambs inoculated with nonlytic OvLV isolates only mild LIP lesions developed, without concurrent mammary gland or joint lesions. Bronchoalveolar lavage samples from OvLV-diseased lambs contained on average 1.5-fold more numbers of total leukocytes, and 4-fold more numbers of lymphocytes, compared with bronchoalveolar lavage samples of normal lambs. Monoclonal antibodies to ovine lymphocyte surface markers showed that the SBU-T8+ lymphocyte (CD 8 equivalent) was the predominant lymphocyte subset (mean of 65% of total lavaged lymphocytes) in bronchoalveolar lavage samples of 3 diseased lambs. Ovine lentivirus was reisolated from multiple tissues of both groups of OvLV-inoculated lambs, but the percentage of individual tissues infected was greater in lambs inoculated with the lytic viral isolate. Control lambs had no lesions and failed to produce OvLV-specific antibodies or yield OvLV from tissues. All OvLV-inoculated lambs produced either low or undetectable serum virus neutralizing antibodies. In contrast, lambs inoculated with either lytic or nonlytic OvLV produced precipitating antibodies to OvLV glycoprotein and group-specific protein. However, initial detection of precipitating antibodies to OvLV glycoprotein was earlier (mean, 5.8 weeks after inoculation) in OvLV-infected lambs in which severe lymphoproliferative disease developed and delayed (mean, 10.2 weeks after inoculation) in OvLV-infected lambs with mild or no lesions. Together, these results suggest that lentivirus isolates produced disease in a virus strain-dependent manner and suggest that humoral immune responses against OvLV failed to prevent lesion development in lentivirus-infected lambs.(ABSTRACT TRUNCATED AT 400 WORDS)