Previous Article | Next Article 
Journal of Virology, December 2004, p. 12951-12963, Vol. 78, No. 23
0022-538X/04/$08.00+0 DOI: 10.1128/JVI.78.23.12951-12963.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
Two Modes of Pseudorabies Virus Neuroinvasion and Lethality in Mice
Elizabeth E. Brittle,
Ashley E. Reynolds, and
L. W. Enquist*
Department of Molecular Biology, Princeton University, Princeton, New Jersey
Received 17 June 2004/
Accepted 6 August 2004
We describe two distinct modes of neuroinvasion and lethality after murine flank inoculation with virulent and attenuated strains of pseudorabies virus (PRV). Mice infected with virulent (e.g., PRV-Becker, PRV-Kaplan, or PRV-NIA3) strains self-mutilate their flank skin in response to virally induced pruritus, die rapidly with no identifiable symptoms of central nervous system (CNS) infection such as behavioral abnormalities, and have little infectious virus or viral antigen in the brain. In distinct contrast, animals infected with an attenuated PRV vaccine strain (PRV-Bartha) survive approximately three times longer than wild-type PRV-infected animals, exhibit severe CNS abnormalities, and have an abundance of infectious virus in the brain at the time of death. Interestingly, these animals have no skin lesions and do not appear pruritic at any time during infection. The severe pruritus and relatively earlier time until death induced by wild-type PRV infection may reflect the peripheral nervous system (PNS) and immune responses to infection rather than a fatal, virally induced CNS pathology. Based on previously characterized afferent (sensory) and efferent (motor) neuronal pathways that innervate the skin, we deduced that wild-type virulent strains transit through the PNS via both afferent and efferent routes, whereas PRV-Bartha travels by only efferent routes in the PNS en route to the brain.
* Corresponding author. Mailing address: 314 Schultz Laboratory, Department of Molecular Biology, Princeton University, Princeton, NJ 08544. Phone: (609) 258-2415. Fax: (609) 258-1035. E-mail:
lenquist{at}molbio.princeton.edu.
Journal of Virology, December 2004, p. 12951-12963, Vol. 78, No. 23
0022-538X/04/$08.00+0 DOI: 10.1128/JVI.78.23.12951-12963.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
This article has been cited by other articles:
-
McGraw, H. M., Friedman, H. M.
(2009). Herpes Simplex Virus Type 1 Glycoprotein E Mediates Retrograde Spread from Epithelial Cells to Neurites. J. Virol.
83: 4791-4799
[Abstract]
[Full Text]
-
Curanovic, D., Lyman, M. G., Bou-Abboud, C., Card, J. P., Enquist, L. W.
(2009). Repair of the UL21 Locus in Pseudorabies Virus Bartha Enhances the Kinetics of Retrograde, Transneuronal Infection In Vitro and In Vivo. J. Virol.
83: 1173-1183
[Abstract]
[Full Text]
-
Brittle, E. E., Wang, F., Lubinski, J. M., Bunte, R. M., Friedman, H. M.
(2008). A Replication-Competent, Neuronal Spread-Defective, Live Attenuated Herpes Simplex Virus Type 1 Vaccine. J. Virol.
82: 8431-8441
[Abstract]
[Full Text]
-
Brukman, A., Enquist, L. W.
(2006). Pseudorabies Virus EP0 Protein Counteracts an Interferon-Induced Antiviral State in a Species-Specific Manner. J. Virol.
80: 10871-10873
[Abstract]
[Full Text]
-
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]
-
Olsen, L. M., Ch'ng, T. H., Card, J. P., Enquist, L. W.
(2006). Role of Pseudorabies Virus Us3 Protein Kinase during Neuronal Infection.. J. Virol.
80: 6387-6398
[Abstract]
[Full Text]
-
Klopfleisch, R., Klupp, B. G., Fuchs, W., Kopp, M., Teifke, J. P., Mettenleiter, T. C.
(2006). Influence of pseudorabies virus proteins on neuroinvasion and neurovirulence in mice.. J. Virol.
80: 5571-5576
[Abstract]
[Full Text]
-
Paulus, C., Sollars, P. J., Pickard, G. E., Enquist, L. W.
(2006). Transcriptome Signature of Virulent and Attenuated Pseudorabies Virus-Infected Rodent Brain. J. Virol.
80: 1773-1786
[Abstract]
[Full Text]
-
Schwartz, J. A., Brittle, E. E., Reynolds, A. E., Enquist, L. W., Silverstein, S. J.
(2006). UL54-Null Pseudorabies Virus Is Attenuated in Mice but Productively Infects Cells in Culture. J. Virol.
80: 769-784
[Abstract]
[Full Text]
-
Wang, F., Tang, W., McGraw, H. M., Bennett, J., Enquist, L. W., Friedman, H. M.
(2005). Herpes Simplex Virus Type 1 Glycoprotein E Is Required for Axonal Localization of Capsid, Tegument, and Membrane Glycoproteins. J. Virol.
79: 13362-13372
[Abstract]
[Full Text]
-
Pomeranz, L. E., Reynolds, A. E., Hengartner, C. J.
(2005). Molecular Biology of Pseudorabies Virus: Impact on Neurovirology and Veterinary Medicine. Microbiol. Mol. Biol. Rev.
69: 462-500
[Abstract]
[Full Text]
-
Ch'ng, T. H., Enquist, L. W.
(2005). Efficient Axonal Localization of Alphaherpesvirus Structural Proteins in Cultured Sympathetic Neurons Requires Viral Glycoprotein E. J. Virol.
79: 8835-8846
[Abstract]
[Full Text]
-
del Rio, T., DeCoste, C. J., Enquist, L.W.
(2005). Actin Is a Component of the Compensation Mechanism in Pseudorabies Virus Virions Lacking the Major Tegument Protein VP22. J. Virol.
79: 8614-8619
[Abstract]
[Full Text]