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Journal of Virology, March 1999, p. 1795-1801, Vol. 73, No. 3
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Immune Response-Mediated Protection of Adult but Not Neonatal Mice from Neuron-Restricted Measles Virus Infection and Central Nervous System Disease

Diane M. P. Lawrence, Melinda M. Vaughn, Alec R. Belman, Joan S. Cole, and Glenn F. Rall*

The Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111

Received 16 September 1998/Accepted 11 November 1998

In many cases of neurological disease associated with viral infection, such as measles virus (MV)-induced subacute sclerosing panencephalitis in children, it is unclear whether the virus or the antiviral immune response within the brain is the cause of disease. MV inoculation of transgenic mice expressing the human MV receptor, CD46, exclusively in neurons resulted in neuronal infection and fatal encephalitis within 2 weeks in neonates, while mice older than 3 weeks of age were resistant to both infection and disease. At 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 lymphocyte deficiency did not affect the outcome of disease in neonates, but adult CD46+ RAG-2- mice were much more susceptible to both neuronal infection and central nervous system disease than their immunocompetent littermates. These results indicate that CD46-dependent MV infection of neurons, rather than the antiviral immune response in the brain, produces neurological disease in this model system and that immunocompetent adult mice, but not immunologically compromised or immature mice, are protected from infection.

* Corresponding author. Mailing address: Institute for Cancer Research, Fox Chase Cancer Center, 7701 Burholme Ave., Philadelphia, PA 19111. Phone: (215) 728-3617. Fax: (215) 728-3616. E-mail: gf_rall{at}fccc.edu.

Journal of Virology, March 1999, p. 1795-1801, Vol. 73, No. 3
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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