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Journal of Virology, May 1999, p. 4004-4008, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Jaagsiekte Retrovirus Is Widely Distributed both in T and B Lymphocytes and in Mononuclear Phagocytes of Sheep with Naturally and Experimentally Acquired Pulmonary Adenomatosis

Martin J. Holland,1,dagger Massimo Palmarini,1,Dagger Mercedes Garcia-Goti,2 Lorenzo Gonzalez,2,§ Iain McKendrick,3 Marcelo de las Heras,4 and J. Michael Sharp1,*

Moredun Research Institute, Pentlands Science Park, Midlothian,1 and Biomathematics & Statistics Scotland (Bioss), Edinburgh,3 United Kingdom, and Department of Veterinary Pathology, Servicio de Investigacion y Mejora Agraria, Derio,2 and Department of Veterinary Pathology, Faculty of Veterinary Medicine, University of Zaragoza, Zaragoza,4 Spain

Received 13 August 1998/Accepted 25 January 1999

Jaagsiekte sheep retrovirus (JSRV) is a type D retrovirus specifically associated 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 naturally affected animals. To determine the lymphoid target cells of JSRV, CD4+ T cells, CD8+ T cells, B lymphocytes, and adherent cell (macrophage/monocyte) populations were isolated from the mediastinal lymph nodes of naturally affected sheep and lambs inoculated with JSRV. Cells were enriched to high purity and then analyzed for JSRV proviral DNA by heminested PCR, and the proviral burden was quantitated by limiting dilution analysis. JSRV proviral DNA was found in all subsets examined but not in appropriate negative controls. In sheep naturally affected with SPA, JSRV proviral burden was greatest in the adherent cell population. In the nonadherent lymphocyte population, surface immunoglobulin-positive B cells contained the greatest proviral 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 detected in the peripheral blood mononuclear cell (PBMC) population. A kinetic study of JSRV infection in the mediastinal lymphocyte population of newborn lambs inoculated with JSRV found that JSRV proviral DNA could be detected as early as 7 days postinoculation before the onset of pulmonary adenomatosis, although the proviral burden was greatly reduced compared to adult natural 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 cells of sheep and that dissemination precedes tumor formation. Infection of lymphoid tissue, therefore, may play an important role in the pathogenesis of SPA.

* Corresponding author. Mailing address: Moredun Research Institute, International Research Centre, Pentlands Science Park, Bush Loan, Penicuik, Midlothian EH26 0PZ, United Kingdom. Phone: (44) 131-445-5111. Fax: (44) 131-445-6235. E-mail: sharm{at}mri.sari.ac.uk.

dagger Present address: Institute of Cell, Animal and Population Biology, Ashworth Laboratories, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom.

Dagger Present address: Cancer Research Institute, University of California at Irvine, Irvine, CA 92697.

§ Present address: Moredun Research Institute, Pentlands Science Park, Midlothian EH26 0PZ, United Kingdom.

Journal of Virology, May 1999, p. 4004-4008, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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