Experimental Visna in Icelandic Sheep: The Prototype Lentiviral Infection

A brief review of experimental infection of Icelandic sheep following intracerebral inoculation of neurotropic strains of visna virus is presented. In vivo replication of the virus is restricted, so that some cells carry the deoxyribonucleic acid provirus as an unexpressed genome. This cellular restriction plays a major role in the slow progression of the infection, abetted by neutralizing antibody in serum and spinal fluid. The latent provirus maintains the viral genome in the presence of an active immune response, since immune surveillance cannot reocgnize cells that are not synthesizing viral antigens. Infected Icelandic sheep experience two types of diseases of the central nervous system: a subclinical subacute encephalitis begins within weeks of infection in most sheep; and at irregular intervals from 0.5-8 years after infection, clinical paresis develops in the majority of Icelandic sheep and is accompanied by discrete focal demyelinating lesions in the spinal cord. The subacute encephalomyelitis is probably mediated by an antiviral cellular immune response, whereas the pathogenesis of the focal demyelinating lesions is still obscure. During persistent infection there is some selection for neutralization-resistant antigenic variants of the infecting serotype, and these are isolated at a frequency of ∼15%. However, variants do not replace the infecting serotype, and antigenic drift does not appear essential for persistence of visna virus or for the occurrence of demyelinating lesions.