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 Askovic, S.
Right arrow Articles by Portis, J. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Askovic, S.
Right arrow Articles by Portis, J. L.

 Previous Article  |  Next Article 

Journal of Virology, January 2000, p. 465-473, Vol. 74, No. 1
0022-538X/0/$04.00+0

Brain Infection by Neuroinvasive but Avirulent Murine Oncornaviruses

Srdjan Askovic',* Frank J. McAtee, Cynthia Favara, and John L. Portis

Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 59840

Received 6 July 1999/Accepted 27 September 1999

The chimeric murine oncornavirus FrCasE causes a rapidly progressive noninflammatory spongiform encephalomyelopathy after neonatal inoculation. The virus was constructed by the introduction of pol-env sequences from the wild mouse virus CasBrE into the genome of a neuroinvasive but nonneurovirulent strain of Friend murine leukemia virus (FMuLV), FB29. Although the brain infection by FrCasE as well as that by other neurovirulent murine retroviruses has been described in detail, little attention has been paid to the neuroinvasive but nonneurovirulent viruses. The purpose of the present study was to compare brain infection by FrCasE with that by FB29 and another nonneurovirulent virus, F43, which contains pol-env sequences from FMuLV 57. Both FB29 and F43 infected the same spectrum of cell types in the brain as that infected by FrCasE, including endothelial cells, microglia, and populations of neurons which divide postnatally. Viral burdens achieved by the two nonneurovirulent viruses in the brain were actually higher than that of FrCasE. The widespread infection of microglia by the two nonneurovirulent viruses is notable because it is infection of these cells by FrCasE which is thought to be a critical determinant of its neuropathogenicity. These results indicate that although the sequence of the envelope gene determines neurovirulence, this effect appears to operate through a mechanism which does not influence either viral tropism or viral burden in the brain. Although all three viruses exhibited similar tropism for granule neurons in the cerebellar cortex, there was a striking difference in the distribution of envelope proteins in those cells in vivo. The FrCasE envelope protein accumulated in terminal axons, whereas those of FB29 and F43 remained predominantly in the cell bodies. These observations suggest that differences in the intracellular sorting of these proteins may exist and that these differences appear to correlate with neurovirulence.

* Corresponding author. Mailing address: Rocky Mountain Laboratories, 903 South 4th St., Hamilton, MT 59840. Phone: (406) 363-9359. Fax: (406) 363-9286. E-mail: saskovic{at}nih.gov.

Journal of Virology, January 2000, p. 465-473, Vol. 74, No. 1
0022-538X/0/$04.00+0


This article has been cited by other articles:

  • Portis, J. L., Askovich, P., Austin, J., Gutierrez-Cotto, Y., McAtee, F. J. (2009). The Degree of Folding Instability of the Envelope Protein of a Neurovirulent Murine Retrovirus Correlates with the Severity of the Neurological Disease. J. Virol. 83: 6079-6086 [Abstract] [Full Text]  
  • Case, L. K., Petell, L., Yurkovetskiy, L., Purdy, A., Savage, K. J., Golovkina, T. V. (2008). Replication of Beta- and Gammaretroviruses Is Restricted in I/LnJ Mice via the Same Genetic Mechanism. J. Virol. 82: 1438-1447 [Abstract] [Full Text]  
  • Clase, A. C., Dimcheff, D. E., Favara, C., Dorward, D., McAtee, F. J., Parrie, L. E., Ron, D., Portis, J. L. (2006). Oligodendrocytes Are a Major Target of the Toxicity of Spongiogenic Murine Retroviruses. Am. J. Pathol. 169: 1026-1038 [Abstract] [Full Text]  
  • Peterson, K. E., Hughes, S., Dimcheff, D. E., Wehrly, K., Chesebro, B. (2004). Separate Sequences in a Murine Retroviral Envelope Protein Mediate Neuropathogenesis by Complementary Mechanisms with Differing Requirements for Tumor Necrosis Factor Alpha. J. Virol. 78: 13104-13112 [Abstract] [Full Text]  
  • Dimcheff, D. E., Faasse, M. A., McAtee, F. J., Portis, J. L. (2004). Endoplasmic Reticulum (ER) Stress Induced by a Neurovirulent Mouse Retrovirus Is Associated with Prolonged BiP Binding and Retention of a Viral Protein in the ER. J. Biol. Chem. 279: 33782-33790 [Abstract] [Full Text]  
  • Murphy, S. L., Honczarenko, M. J., Dugger, N. V., Hoffman, P. M., Gaulton, G. N. (2004). Disparate Regions of Envelope Protein Regulate Syncytium Formation versus Spongiform Encephalopathy in Neurological Disease Induced by Murine Leukemia Virus TR. J. Virol. 78: 8392-8399 [Abstract] [Full Text]  
  • Dimcheff, D. E., Askovic, S., Baker, A. H., Johnson-Fowler, C., Portis, J. L. (2003). Endoplasmic Reticulum Stress Is a Determinant of Retrovirus-Induced Spongiform Neurodegeneration. J. Virol. 77: 12617-12629 [Abstract] [Full Text]  
  • Hook, L. M., Jude, B. A., Ter-Grigorov, V. S., Hartley, J. W., Morse, H. C. III, Trainin, Z., Toder, V., Chervonsky, A. V., Golovkina, T. V. (2002). Characterization of a Novel Murine Retrovirus Mixture That Facilitates Hematopoiesis. J. Virol. 76: 12112-12122 [Abstract] [Full Text]  
  • Askovic, S., Favara, C., McAtee, F. J., Portis, J. L. (2001). Increased Expression of MIP-1{alpha} and MIP-1{beta} mRNAs in the Brain Correlates Spatially and Temporally with the Spongiform Neurodegeneration Induced by a Murine Oncornavirus. J. Virol. 75: 2665-2674 [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»