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Journal of Virology, July 2008, p. 6150-6160, Vol. 82, No. 13
0022-538X/08/$08.00+0 doi:10.1128/JVI.00106-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

,
Susan J. Bender,
Ming Ming Chua,
Richard Watson, and
Susan R. Weiss*
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104
Received 15 January 2008/ Accepted 6 April 2008
Virus-specific CD8+ T cells are critical for protection against neurotropic coronaviruses; however, central nervous system (CNS) infection with the recombinant JHM (RJHM) strain of mouse hepatitis virus (MHV) elicits a weak CD8+ T-cell response in the brain and causes lethal encephalomyelitis. An adoptive transfer model was used to elucidate the kinetics of CD8+ T-cell priming during CNS infection with RJHM as well as with two MHV strains that induce a robust CD8+ T-cell response (RA59 and SJHM/RA59, a recombinant A59 virus expressing the JHM spike). While RA59 and SJHM/RA59 infections resulted in CD8+ T-cell priming within the first 2 days postinfection, RJHM infection did not lead to proliferation of naïve CD8+ T cells. While all three viruses replicated efficiently in the brain, only RA59 and SJHM/RA59 replicated to appreciable levels in the cervical lymph nodes (CLN), the site of T-cell priming during acute CNS infection. RJHM was unable to suppress the CD8+ T-cell response elicited by RA59 in mice simultaneously infected with both strains, suggesting that RJHM does not cause generalized immunosuppression. RJHM was also unable to elicit a secondary CD8+ T-cell response in the brain following peripheral immunization against a viral epitope. Notably, the weak CD8+ T-cell response elicited by RJHM was unique to CNS infection, since peripheral inoculation induced a robust CD8+ T-cell response in the spleen. These findings suggest that the failure of RJHM to prime a robust CD8+ T-cell response during CNS infection is likely due to its failure to replicate in the CLN.
Published ahead of print on 16 April 2008.
Present address: Wadsworth Center, 5094A David Axelrod Institute, 120 New Scotland Avenue, Albany, NY 12208.
K.C.M. and S.J.B. contributed equally to this work.
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