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The humoral and cellular immune responses of goats experimentally infected with an ovine isolate of parainfluenza type 3 virus (PI-3) were examined. Virus neutralization and enzyme-linked immunosorbent assays were used to determine antibody in the serum and CSF. Lymphocyte stimulation, measured by [3H]thymidine incorporation into peripheral blood leukocytes, was used to determine cellular responses to phytomitogens and virus. There were significant suppression of peripheral blood leukocyte responses to T-cell mitogens early in the course of infection and delayed onset of virus-specific cell-mediated immunity. Delay in antibody formation did not occur. The suppression of mitogen response has been reported with other paramyxovirus infections. The importance of the suppressed cellular immune response for potentiating other infective agents is discussed.

Visna-maedi of sheep and arthritis encephalitis of goats are slowly progressive diseases caused by serologically related lentiviruses. Lesions are inflammatory and can occur at one or many sites including the central nervous system, lungs, joints, and mammary glands. The viruses replicate in macrophages, and in the animal large numbers of infected macrophages can be obtained from inflamed tissues. To study virus-macrophage interactions we transformed sheep alveolar macrophages, which are natural virus target cells, with simian virus 40 and produced a macrophage cell line. The transformed cells grew into density-dependent monolayers and were subcultured after trypsin dissociation. They maintained histochemical and physiologic properties of macrophages as well as the ability to support replication of the lentiviruses. Rabbit antisera to these cells reacted with blood monocytes and only selected populations of tissue macrophages, including those in lung, synovium, mammary gland, and spleen. Microglia, Kupffer cells, and connective tissue histiocytes were not recognized by the sera. Since the tissues in which virus localizes in infected animals are the same as those recognized by the sera, the antimacrophage serum may provide an immunologic marker for virus-susceptible macrophages in the animal.

Lentiviruses, which cause arthritis-encephalitis and maedi-visna in goats and sheep, respectively, cause persistent infections in these animals. The viruses replicate productively at low levels in macrophages in diseased organs such as the "maedi lung" and nonproductively in other cell types such as leukocytes in peripheral blood. Nonproductive infections become productive during in vitro cultivation of the cells. This study showed that monocytes were the only cells in the peripheral blood leukocytes of an infected animal in which virus was detected and that virus activation occurred only when these cells matured into macrophages. Only a minute fraction of cultured monocytes matured into macrophages, and viral infectivity was associated exclusively with this fraction. Antiglobulin-coated glass wool fragments were lethal for monocyte macrophages because of toxic phagocytosis, but had no effect on B or T lymphocytes. The simultaneous addition of the glass fragments and leukocytes to culture dishes resulted in no macrophage maturation and no virus production. The addition of the fragments to virus-producing macrophages caused the death of the cells and a decline in virus production. Virus production in less avidly phagocytic cells was unaffected by the glass. Thus, although macrophages may be permissive for virus replication, one mechanism for restricted virus expression in vivo may be physiological factors controlling the maturation of these cells.

A herd of 15 dairy goats with a previous history of neurological disease in kids was screened for caprine arthritis-encephalitis (CAE) virus infection. Virus was isolated from the PBL of all animals as well as milk from lactating does. All animals had antibody detected by ELISA and gel immuno-diffusion. Two animals from this herd were examined for responses to infection. One was an adult female with poor milk production and the other was a 3-month-old female kid which developed acute neurological disease. Both animals had a chronic mastitis compatible with a viral aetiology, and CAE virus was isolated from the mammary tissue of both. The mammary gland must thus be considered an important target organ for virus infection and dissemination.