Slow Virus Infection: Replication and Mechanisms of Persistence of Visna Virus in Sheep

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Abstract
The influence of the age and immune status of the host on the slow replication and persistence of visna virus in sheep was studied. Twenty-five randomly bred fetal American lambs were inoculated intracerebrally with visna virus. Eight of these fetuses were immunosuppressed by thymectomy and antiserum to lymphocytes before inoculation. 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 finding 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 maturation or immune status of the host. In addition, virus isolated from the peripheral blood leukocytes of a sheep one year 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. This distinction suggested that a major antigenic shift of the agent had occurred and provided another mechanism for the maintenance of the persistent infection.