Ovine lentivirus expression and disease. Virus replication, but not entry, is restricted to macrophages of specific tissues.

To better define the relationship between lentivirus infection and lymphoproliferative or inflammatory disease, we studied postmortem specimens of 38 sheep naturally infected with ovine lentivirus (OvLV) and with different clinical manifestations of OvLV-associated disease. Immunohistochemistry, in situ hybridization, and virus isolation were used to localize viral protein, viral RNA, and infectious virus to specific cells and tissues. Viral protein or infectious virus was found in cells morphologically and histochemically compatible with macrophages (M phi s), but only in lung, bone marrow, mammary gland, lymph node, spleen, synovium, brain, and spinal cord, frequently in association with lymphocyte infiltrates. In contrast, viral RNA was found in a variety of cell types, including epithelium, M phi s, and M phi-like cells, and in a wider range of tissues, with or without OvLV-associated lesions. In summary, these findings suggest that in vivo: 1), OvLV can enter a variety of cell types, 2), productive infection is restricted to cells of M phi lineage, and 3), cells expressing viral proteins are limited to specific tissues, those associated with OvLV-induced diseases.