Role of the individual interferon systems and specific immunity in mice in controlling systemic dissemination of attenuated pseudorabies virus infection.

The importance of each of the two interferon (IFN) systems in impeding herpesvirus replication and in stimulating virus-specific lymphocytes to control an acute systemic infection is not completely understood. To further our knowledge, pseudorabies virus, attenuated by deletion of the glycoprotein E gene to impair its neurovirulence and by deletion of the thymidine kinase gene (gE-TK-PRV), was used to infect wild-type 129Sv/Ev and congenic mice with immune system-associated genetic deficiencies. Mice with mature B and T lymphocytes but lacking either one or both functional receptors for members of each of the two IFN families were infected with gE-TK-PRV. At 3 and 7 but not 14 days after infection, replicating gE-TK-PRV could be isolated only from livers or spleens of mice lacking the receptors for both IFN families, and these mice survived the infection. Therefore, functional IFN receptors were not required to induce a protective immune response against an acute infection with gE-TK-PRV. Furthermore, PRV-specific antibodies of all immunoglobulin G isotypes were produced in these mice. Mice without mature B and T lymphocytes and lacking either one or both functional receptors for members of each of the two IFN families were also infected with gE-TK-PRV. Three days after infection, replicating virus could be isolated only from mice lacking both mature B and T lymphocytes and functional IFN receptors, and these mice were not able to clear the virus. We present evidence that mice with an intact gamma IFN system but without mature B and T cells were able to prevent systemic dissemination of gE-TK-PRV.

Does infection initiate Graves disease? A population based 10 year study.

In order to detect whether micro-organisms could initiate the autoimmune process in Graves' disease we have studied the temporal and spatial distribution of 857 cases of hyperthyroidism occurring in a community over ten years. Cases were identified through biochemistry laboratory records and following the exclusion of patients with toxic nodular goitre or with insufficient clinical data there were 599 with Graves' disease--an average annual incidence of 15.9 per 100,000. There was a tendency for cases to present in the summer months. The reported onset of symptoms, however, peaked in December and June. There was no evidence of clustering of cases in space and time using two different statistical methods. Incidence rates doubled between 1976 and 1980 and then declined--a trend that could neither be explained by changes in laboratory or clinical diagnosis nor did it correlate with any pattern of microbial disease in the area. We conclude that it is unlikely that infections that behave in an epidemic manner have a causative role in triggering Graves' disease.