JVI Accepts, published online ahead of print on 16 April 2008

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J. Virol. doi:10.1128/JVI.00106-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Priming of CD8+ T cells during central nervous system infection with a murine coronavirus is strain-dependent

Katherine C. MacNamara, Susan J. Bender, Ming Ming Chua, Richard Watson, and Susan R. Weiss^*

Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104

^* To whom correspondence should be addressed. Email: weisssr{at}mail.med.upenn.edu.

Virus-specific CD8+ T cells are critical for protection against neurotropic coronaviruses; however, 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 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 post-infection, 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 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, as peripheral inoculation induced a robust CD8+ T cell response in the spleen. These findings suggest that RJHM fails to prime a robust CD8+ T cell response during CNS infection likely due to its failure to replicate in the CLN.