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Journal of Virology, January 2004, p. 585-594, Vol. 78, No. 2
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.2.585-594.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

CXC Chemokine Ligand 10 Controls Viral Infection in the Central Nervous System: Evidence for a Role in Innate Immune Response through Recruitment and Activation of Natural Killer Cells

Matthew J. Trifilo,1 Cynthia Montalto-Morrison,2 Linda N. Stiles,1 Kelley R. Hurst,2 Jenny L. Hardison,1 Jerry E. Manning,1 Paul S. Masters,2 and Thomas E. Lane1*

Department of Molecular Biology and Biochemistry, University of California, Irvine, California 92697-3900,1 Wadsworth Center, New York State Department of Health, Albany, New York 122012

Received 23 July 2003/ Accepted 19 September 2003

How chemokines shape the immune response to viral infection of the central nervous system (CNS) has largely been considered within the context of recruitment and activation of antigen-specific lymphocytes. However, chemokines are expressed early following viral infection, suggesting an important role in coordinating innate immune responses. Herein, we evaluated the contributions of CXC chemokine ligand 10 (CXCL10) in promoting innate defense mechanisms following coronavirus infection of the CNS. Intracerebral infection of RAG1-/- mice with a recombinant CXCL10-expressing murine coronavirus (mouse hepatitis virus) resulted in protection from disease and increased survival that correlated with a significant increase in recruitment and activation of natural killer (NK) cells within the CNS. Accumulation of NK cells resulted in a reduction in viral titers that was dependent on gamma interferon secretion. These results indicate that CXCL10 expression plays a pivotal role in defense following coronavirus infection of the CNS by enhancing innate immune responses.

* Corresponding author. Mailing address: Department of Molecular Biology and Biochemistry, 3205 McGaugh Hall, University of California, Irvine, CA 92697-3900. Phone: (949) 824-5878. Fax: (949) 824-8551. E-mail: tlane{at}uci.edu.

Journal of Virology, January 2004, p. 585-594, Vol. 78, No. 2
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.2.585-594.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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