The Pathogenesis of Avirulent Semliki Forest Virus Infections in Athymic Nude Mice

Neurovirology Unit, The Rayne Institute, St Thomas' Hospital, London SE1 7EH the * Microbiological Research Establishment, Porton Down, Salisbury, Wilts., U.K. The course and outcome of intraperitoneally induced infections with the avirulent strain A7(74) of Semliki Forest virus have been studied in athymic ‘nude’ (nu/nu) mice, their heterozygous (nu/+) littermates and conventional Swiss A 2 G mice. The main distinguishing characteristics of the infection in the nu/nu mice were the persistence of virus in the brain after an initial phase of incomplete virus clearance and the apparent establishment of a secondary phase of virus replication in the brain which was associated with a falling neutralizing antibody response. This secondary phase of virus replication persisted until at least the 28th day after inoculation. In addition the typical histological lesions of encephalitis induced by this virus were rare and focal demyelination, which occurred at a light microscopy level in up to 26% of nu/+ and Swiss A 2 G mice, was not observed. It is suggested that in immunocompetent mice the development of lesions including demyelination may be a result of an immunopathological response to virus infection which is related to the presence of thymus derived lymphocytes. Received 17 May 1978; accepted 27 June 1978.