This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Murphy, S. L. Articles by Gaulton, G. N. Search for Related Content PubMed PubMed Citation Articles by Murphy, S. L. Articles by Gaulton, G. N.

Disparate Regions of Envelope Protein Regulate Syncytium Formation versus Spongiform Encephalopathy in Neurological Disease Induced by Murine Leukemia Virus TR

Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104,¹ Center for Blood Research, Boston, Massachusetts 02115,² Research Service, Veterans Administration Maryland Health Care System, and Department of Neurology, University of Maryland, Baltimore, Maryland 21201³

Received 22 December 2003/ Accepted 5 April 2004

The murine leukemia virus (MLV) TR1.3 provides an excellent model to study the wide range of retrovirus-induced central nervous system (CNS) pathology and disease. TR1.3 rapidly induces thrombotic events in brain microvessels and causes cell-specific syncytium formation of brain capillary endothelial cells (BCEC). A single amino acid substitution, W102G, in the MLV envelope protein (Env) regulates the pathogenic effects. The role of Env in determining this disease phenotype compared to the induction of spongiform encephalomyelitis with a longer latency, as seen in several other MLV and in human retroviruses, was determined by studying in vitro-attenuated TR1.3. Virus cloned from this selection, termed TRM, induced progressive neurological disease characterized by ataxia and paralysis and the appearance of spongiform neurodegeneration throughout the brain stem and spinal cord. This disease was associated with virus replication in both BCEC and highly ramified glial cells. TRM did not induce syncytium formation, either in vivo or in vitro. Sequence and mutational analyses demonstrated that TRM contained a reversion of Env G102W but that neurological disease mapped to the single amino acid substitution Env S159P. The results demonstrate that single nucleotide changes within disparate regions of Env control dramatically different CNS disease patterns.

This article has been cited by other articles:

• Murphy, S. L., Gaulton, G. N. (2007). TR1.3 Viral Pathogenesis and Syncytium Formation Are Linked to Env-Gag Cooperation. J. Virol. 81: 10777-10785 [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]