title: 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)
authors.affiliation: Department of Pathology, Colorado State University, College of Veterinary Medicine and Biomedical Sciences, Fort Collins.
authors.forename: M D
authors.initials: MD
authors.lastname: Lairmore
authors.forename: J M
authors.initials: JM
authors.lastname: Poulson
authors.forename: T A
authors.initials: TA
authors.lastname: Adducci
authors.forename: J C
authors.initials: JC
authors.lastname: DeMartini
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005260:Female; D006041:Goats; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology; D008232:Lymphoproliferative Disorders / Q000382:microbiology / Q000473:pathology / Q000662:veterinary*; D008297:Male; D012190:Retroviridae / Q000254:growth & development / Q000472:pathogenicity*; D012756:Sheep / Q000382:microbiology*; D012757:Sheep Diseases / Q000382:microbiology* / Q000473:pathology