Pathogenesis of visna. I. Sequential virologic, serologic, and pathologic studies.

A total of 56 Icelandic sheep were infected with visna virus by intracerebral injection of strain 1514 and the course of infection was followed for 12 months. Virus was isolated from more than 90 per cent of the animals, primarily from central nervous system and lymphoid tissues. However, titers of free infectious virus were minimal and virus isolation often required the use of tissue explants. All sheep raised serum-neutralizing and complement-fixing antibodies beginning 1 to 3 months after infection. Differences in neutralization titers against the infecting strain (1514) and a reference strain (796) suggested that antigenic drift might occur during prolonged infection. High cerebrospinal fluid neutralization titers in the spinal fluid indicated local antibody production in the central nervous system. Although the incidence of clinical disease during the 1st year of infection was less that 10 per cent, approximately 80 per cent of the sheep examined had central nervous system histologic lesions of variable severity, which were marked 1 month after infection with little progression during the subsequent year. There was a striking correlation between the severity of central nervous system lesions and the frequency of virus isolations from all tissues. These observations provide detailed base line data on visna infection, suggest some of the mechanisms responsible for the persistence of infection and for the slowness and irregularity of disease occurrence, and form the basis for further experiments on the role of immunologic mechanisms in the pathogenesis of this slow infection.