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Journal of Virology, May 2002, p. 4497-4506, Vol. 76, No. 9
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.9.4497-4506.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Immune-Mediated Protection from Measles Virus-Induced Central Nervous System Disease Is Noncytolytic and Gamma Interferon Dependent

Catherine E. Patterson, Diane M. P. Lawrence,,{dagger} Lisa A. Echols, and Glenn F. Rall*

Division of Basic Science, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111

Received 27 November 2001/ Accepted 17 January 2002

Neurons of the mammalian central nervous system (CNS) are an essential and largely nonrenewable cell population. Thus, virus infections that result in neuronal depletion, either by virus-mediated cell death or by induction of the cytolytic immune response, could cause permanent neurological impairment of the host. In a transgenic mouse model of measles virus (MV) infection of neurons, we have previously shown that the host T-cell response was required for resolution of infection in susceptible adult mice. In this report, we show that this protective response did not result in neuronal death, even during the peak of T-cell infiltration into the brain parenchyma. When susceptible mice were intercrossed with specific immune knockout mice, a critical role for gamma interferon (IFN-{gamma}) was identified in protection against MV infection and CNS disease. Moreover, the addition of previously activated splenocytes or recombinant murine IFN-{gamma} to MV-infected primary neurons resulted in the inhibition of viral replication in the absence of neuronal death. Together, these data support the hypothesis that the host immune response can promote viral clearance without concomitant neuronal loss, a process that appears to be mediated by cytokines.

* Corresponding author. Mailing address: The Fox Chase Cancer Center, 7701 Burholme Ave., Philadelphia, PA 19111. Phone: (215) 728-3617. Fax: (215) 728-2412. E-mail: gf_rall{at}fccc.edu.

{dagger} Present address: Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Md.

Journal of Virology, May 2002, p. 4497-4506, Vol. 76, No. 9
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.9.4497-4506.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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