Immune response-mediated protection of adult but not neonatal mice from neuron-restricted measles virus infection and central nervous system disease

In many cases of neurological disease associated with viral infection, such as measles virus (MV)-induced subacute sclerosing panencephalitis in child ren, it is unclear whether the virus or the antiviral immune response withi n the brain is the cause of disease. MV inoculation of transgenic mice expr essing the human MV receptor, CD46, exclusively in neurons resulted in neur onal infection and fatal encephalitis within 2 weeks in neonates, while mic e older than 3 weeks of age were resistant to both infection and disease. A t all ages, T lymphocytes infiltrated the brain in response to inoculation. To determine the role of lymphocytes in disease progression, CD46(+) mice were back crossed to T- and B-cell-deficient RAG-2 knockout mice. The lymph ocyte deficiency did not affect the outcome of disease in neonates, hut adu lt CD46(+) RAG-2(-) mice were much more susceptible to both neuronal infect ion and central nervous system disease than their immunocompetent littermat es. These results indicate that CD46-dependent MV infection of neurons, rat her than the antiviral immune response in the brain, produces neurological disease in this model system and that immunocompetent adult mice, but not i mmunologically compromised or immature mice, are protected from infection.