This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Schäfer, A.
Right arrow Articles by Johnston, R. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Schäfer, A.
Right arrow Articles by Johnston, R. E.

 Previous Article  |  Next Article 

Journal of Virology, May 2009, p. 4275-4286, Vol. 83, No. 9
0022-538X/09/$08.00+0     doi:10.1128/JVI.02383-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Replicon Particles of Venezuelan Equine Encephalitis Virus as a Reductionist Murine Model for Encephalitis{triangledown}

Alexandra Schäfer,* Alan C. Whitmore, Jennifer L. Konopka,{dagger} and Robert E. Johnston

Department of Microbiology and Immunology, Carolina Vaccine Institute, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599

Received 17 November 2008/ Accepted 5 February 2009

Venezuelan equine encephalitis virus (VEE) replicon particles (VRP) were used to model the initial phase of VEE-induced encephalitis in the mouse brain. VRP can target and infect cells as VEE, but VRP do not propagate beyond the first infected cell due to the absence of the structural genes. Direct intracranial inoculation of VRP into mice induced acute encephalitis with signs similar to the neuronal phase of wild-type VEE infection and other models of virus-induced encephalitis. Using the previously established VRP-mRNP tagging system, a new method to distinguish the host responses in infected cells from those in uninfected bystander cell populations, we detected a robust and rapid innate immune response in the central nervous system (CNS) by infected neurons and uninfected bystander cells. Moreover, this innate immune response in the CNS compromised blood-brain barrier integrity, created an inflammatory response, and directed an adaptive immune response characterized by proliferation and activation of microglia cells and infiltration of inflammatory monocytes, in addition to CD4+ and CD8+ T lymphocytes. Taken together, these data suggest that a naïve CNS has an intrinsic potential to induce an innate immune response that could be crucial to the outcome of the infection by determining the composition and dynamics of the adaptive immune response. Furthermore, these results establish a model for neurotropic virus infection to identify host and viral factors that contribute to invasion of the brain, the mechanism(s) whereby the adaptive immune response can clear the infection, and the role of the host innate response in these processes.

* Corresponding author. Mailing address: Carolina Vaccine Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599. Phone: (919) 966-4026. Fax: (919) 843-6924. E-mail: aschaefe{at}email.unc.edu

{triangledown} Published ahead of print on 18 February 2009.

{dagger} Present address: Lamb Center for Pediatric Research, Vanderbilt University Medical Center, Nashville, TN 37232.

Journal of Virology, May 2009, p. 4275-4286, Vol. 83, No. 9
0022-538X/09/$08.00+0     doi:10.1128/JVI.02383-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Yin, J., Gardner, C. L., Burke, C. W., Ryman, K. D., Klimstra, W. B. (2009). Similarities and Differences in Antagonism of Neuron Alpha/Beta Interferon Responses by Venezuelan Equine Encephalitis and Sindbis Alphaviruses. J. Virol. 83: 10036-10047 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»