Enhanced viral infection in the mouse treated with 6-mercaptopurine

Parenteral inoculation of weanling mice with group B Coxsackie viruses and vaccinia virus resulted in essentially nonlethal infection. Simultaneous treatment of weanling mice with 6-mercaptopurine transformed these infections into lethal episodes. High titers of virus were found in the livers of treated mice, whereas no virus was detected in the livers of infected untreated mice. Similar treatment of mice infected with herpes simplex virus did not significantly increase mortality rate, ordinarily 60 to 80 per cent, but treatment with the purine analogue intensified visceral and systemic viral multiplication. Heightened replication of herpes simplex virus in the liver and brain of treated mice was associated with detectable levels of interferon in these tissues. Interferon was not found in the tissues of infected mice which were unexposed to 6-mercaptopurine. Lymphopenia and absolute neutropenia occurred after 6 days of treatment. Neutralizing antibody was variably present in these experimental infections and occasionally absent from the serum of both untreated as well as treated mice at the latter's death. Neither antibody nor interferon may be as crucial in host resistance to viral infections as delayed hypersensitivity. Furthermore, lymphocellular immunity may be more important in resistance to enteroviral infections than suspected in the past.