Early immune responses in visna, a slow viral disease of sheep

The initial phase of the long incubation period of visna virus infection of sheep was studied by intracerebral inoculation of the 1514 strain of visna virus into 12 Border-Leicester sheep. Cell-free virus was recoverable only during the first two weeks after inoculation. Thereafter, virus could be recovered by cocultivation of cerebrospinal fluid (CSF) cells or peripheral blood leukocytes (PBL) or by explantation of tissues. Virus-specific cell-mediated immunity, measured by stimulation of [3H]thymidine incorporation into PBL and CSF cells, appeared within one week, peaked by two weeks, and then fell to control values by six weeks after inoculation. Histopathologic changes consisted of an initial acute meningoencephalitis changing to a more chronic inflammatory process with the development of dense perivascular infiltration and formation of germinal centers. During the chronic phase virus-neutralizing antibody first appeared in the serum and then in the CSF. We conclude that the initial immune responses of sheep to infection with visna virus are similar to those seen in acute viral infections but fail to eliminate the virus, which eventually results in the slowly evolving neurologic disease visna.