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 Pilipenko, E. V. Articles by Agol, V. I. Search for Related Content PubMed PubMed Citation Articles by Pilipenko, E. V. Articles by Agol, V. I.

 Previous Article  |  Next Article 

Journal of Virology, April 1999, p. 3190-3196, Vol. 73, No. 4
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Distinct Attenuation Phenotypes Caused by Mutations in the Translational Starting Window of Theiler's Murine Encephalomyelitis Virus

Evgeny V. Pilipenko,^1,2 Ekaterina G. Viktorova,¹ Elena V. Khitrina,¹ Svetlana V. Maslova,¹ Nadine Jarousse,³ Michel Brahic,³ and Vadim I. Agol^1,2,*

Institute of Poliomyelitis and Viral Encephalitides, Russian Academy of Medical Sciences, Moscow Region 142782,¹ and Moscow State University, Moscow 119899,² Russia, and Unité des Virus Lents, ERS 572 CNRS, Institut Pasteur, 75724 Paris Cedex 15, France³

Received 10 September 1998/Accepted 8 December 1998

Upon initiation of translation of picornavirus RNA, the ribosome is believed to bind the internal ribosome entry site of the template and then to form a productive complex with a downstream RNA segment, the starting window. The presence or absence of an AUG triplet within the starting window of the RNA of Theiler's murine encephalomyelitis virus (a picornavirus) is known to modulate its neurovirulence. In this study, mutants of this virus in which the starting windows, lying upstream of the viral polyprotein reading frame, had AUGs with different nonoptimal contexts were engineered. Upon intracerebral inoculation of mice, the mutants proved to be partially attenuated, as judged by a significant increase in the dose causing paralysis in 50% of the animals (PD₅₀). Mutants with similar PD₅₀s might differ from one another by eliciting either a severe, fatal tetraplegy or only mild, recoverable neurologic lesions. Some of the mutants triggered a chronic inflammatory reaction in the white matter of the spinal cord in the absence of detectable viral RNA or antigen. Thus, point mutations changing the context of an AUG within the starting window outside the polyprotein reading frame may differently affect the morbidity and mortality caused by a viral infection and may result in distinct attenuation phenotypes.

---

^* Corresponding author. Mailing address: Institute of Poliomyelitis, Moscow Region 142782, Russia. Phone: 7 (95) 439 90 26. Fax: 7 (95) 439 93 21. E-mail: viago{at}ipive.genebee.msu.su.

---

Journal of Virology, April 1999, p. 3190-3196, Vol. 73, No. 4
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

This article has been cited by other articles:

• Florez, P. M., Sessions, O. M., Wagner, E. J., Gromeier, M., Garcia-Blanco, M. A. (2005). The Polypyrimidine Tract Binding Protein Is Required for Efficient Picornavirus Gene Expression and Propagation. J. Virol. 79: 6172-6179 [Abstract] [Full Text]  
• Kumar, A. S. M., Kallio, P., Luo, M., Lipton, H. L. (2003). Amino Acid Substitutions in VP2 Residues Contacting Sialic Acid in Low-Neurovirulence BeAn Virus Dramatically Reduce Viral Binding and Spread of Infection. J. Virol. 77: 2709-2716 [Abstract] [Full Text]  
• Pilipenko, E. V., Pestova, T. V., Kolupaeva, V. G., Khitrina, E. V., Poperechnaya, A. N., Agol, V. I., Hellen, C. U.T. (2000). A cell cycle-dependent protein serves as a template-specific translation initiation factor. Genes Dev. 14: 2028-2045 [Abstract] [Full Text]