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Journal of Virology, February 2006, p. 1773-1786, Vol. 80, No. 4
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.4.1773-1786.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Transcriptome Signature of Virulent and Attenuated Pseudorabies Virus-Infected Rodent Brain

Christina Paulus,^1, Patricia J. Sollars,² Gary E. Pickard,² and Lynn W. Enquist^1*

Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544-1014,¹ Department of Biomedical Sciences, Anatomy and Neurobiology Section, Colorado State University, Fort Collins, Colorado 80523²

Received 13 September 2005/ Accepted 21 November 2005

Mammalian alphaherpesviruses normally establish latent infections in ganglia of the peripheral nervous system in their natural hosts. Occasionally, however, these viruses spread to the central nervous system (CNS), where they cause damaging, often fatal, infections. Attenuated alphaherpesvirus derivatives have been used extensively as neuronal circuit tracers in a variety of animal models. Their circuit-specific spread provides a unique paradigm to study the local and global CNS response to infection. Thus, we systematically analyzed the host gene expression profile after acute pseudorabies virus (PRV) infection of the CNS using Affymetrix GeneChip technology. Rats were injected intraocularly with one of three selected virulent and attenuated PRV strains. Relative levels of cellular transcripts were quantified from hypothalamic and cerebellar tissues at various times postinfection. The number of cellular genes responding to infection correlated with the extent of virus dissemination and relative virulence of the PRV strains. A total of 245 out of 8,799 probe sets, corresponding to 182 unique cellular genes, displayed increased expression ranging from 2- to more than 100-fold higher than in uninfected tissue. Over 60% thereof were categorized as immune, proinflammatory, and other cellular defense genes. Additionally, a large fraction of infection-induced transcripts represented cellular stress responses, including glucocorticoid- and redox-related pathways. This is the first comprehensive in vivo analysis of the global transcriptional response of the mammalian CNS to acute alphaherpesvirus infection. The differentially regulated genes reported here are likely to include potential diagnostic and therapeutic targets for viral encephalitides and other neurodegenerative or neuroinflammatory diseases.

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* Corresponding author. Mailing address: 314 Schultz Laboratory, Department of Molecular Biology, Princeton University, Princeton, NJ08544-1014. Phone: (609) 258-2415. Fax: (609) 258-1035. E-mail: lenquist{at}molbio.princeton.edu.

Present address: Institut für Medizinische Mikrobiologie und Hygiene, Forschungszentrum (FZL), Universität Regensburg, D-93047 Regensburg, Germany.

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Journal of Virology, February 2006, p. 1773-1786, Vol. 80, No. 4
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.4.1773-1786.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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• Brukman, A., Enquist, L. W. (2006). Suppression of the interferon-mediated innate immune response by pseudorabies virus.. J. Virol. 80: 6345-6356 [Abstract] [Full Text]