Jaagsiekte retrovirus is widely distributed both in T and B lymphocytes and in mononuclear phagocytes of sheep with naturally and experimentally acquired pulmonary adenomatosis

Jaagsiekte sheep retrovirus (JSRV) is a type D retrovirus specifically asso ciated with a contagious lung tumor of sheep, sheep pulmonary adenomatosis (SPA), JSRV replicates actively in the transformed epithelial cells of the lung, and JSRV DNA and RNA have been detected in lymphoid tissues of natura lly affected animals. To determine the lymphoid target cells of JSRV, CD4() T cells, CD8(+) T cells, B lymphocytes, and adherent cell (macrophage/mon ocyte) populations were isolated from the mediastinal lymph nodes of natura lly affected sheep and lambs inoculated with JSRV, Cells were enriched to h igh purity and then analyzed for JSRV proviral DNA by heminested PCR, and t he proviral burden was quantitated by limiting dilution analysis. JSRV prov iral DNA was found in all subsets examined but not in appropriate negative controls. In sheep naturally affected with SPA, JSRV proviral burden was gr eatest in the adherent cell population. In the nonadherent lymphocyte popul ation, surface immunoglobulin-positive B cells contained the greatest provi ral burden, while CD4(+) and CD8(+) T cells contained the lowest levels of JSRV proviral DNA, In most of the cases (5 of 8), provirus also could be de tected in the peripheral blood mononuclear cell (PBMC) population. A kineti c study of JSRV infection in the mediastinal lymphocyte population of newbo rn lambs inoculated with JSRV found that JSRV proviral DNA could be detecte d as early as 7 days postinoculation before the onset of pulmonary adenomat osis, although the proviral burden was greatly reduced compared to adult na tural cases. This was reflected in the levels found in PBMC since proviral DNA was detected in 2 of 13 animals. At the early time points studied (7 to 28 days postinoculation) no one subset was preferentially infected, These data indicate that JSRV can infect lymphoid and phagocytic mononuclear cell s of sheep and that dissemination precedes tumor formation. Infection of ly mphoid tissue, therefore, may play an important role in the pathogenesis of SPA.