Slow virus infection: Replication and mechanisms of persistence of visna virus in sheep

The influence of the age and immune status of the host on the slow replication and persistence of visna virus in sheep was studied. A total of 25 randomly bred fetal lambs were inoculated intracerebrally with visna virus; 8 of the fetuses being immunosuppressed by thymectomy and lymphocyte antiserum before inoculation. The fetuses were sacrificed sequentially, and tissues were processed for viral quantitation. No exponential increase of virus occurred in either the normal or immunosuppressed fetuses, and virus was recovered mainly by explantation of tissues. This indicated that the viral genome was present in tissue cells but that the extent of replication in the early phase of infection was restricted by factors unassociated with the maturation or immune status of the host. In addition, virus isolated from the peripheral blood leukocytes of a sheep 1 yr after inoculation was antigenically distinct from the plaque purified virus used for inoculation. Furthermore, the sheep serum neutralized the input virus but not the new isolate. Rhis distinction suggested that a major antigenic shift of the agent had occurred and had provided another mechanism for the maintenance of the persistent infection.