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 Reddi, H. V. Articles by Lipton, H. L. Search for Related Content PubMed PubMed Citation Articles by Reddi, H. V. Articles by Lipton, H. L.

 Previous Article  |  Next Article 

Journal of Virology, August 2004, p. 8909-8916, Vol. 78, No. 16
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.16.8909-8916.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Heparan Sulfate-Independent Infection Attenuates High-Neurovirulence GDVII Virus-Induced Encephalitis

Department of Neurology, Evanston Hospital,¹ Departments of Neurology,³ Microbiology-Immunology,⁴ Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Illinois²

Received 13 January 2004/ Accepted 30 March 2004

The high-neurovirulence Theiler's murine encephalomyelitis virus (TMEV) strain GDVII uses heparan sulfate (HS) as a coreceptor to enter target cells. We report here that GDVII virus adapted to growth in HS-deficient cells exhibited two amino acid substitutions (R3126L and N1051S) in the capsid and no longer used HS as a coreceptor. Infectious-virus yields in CHO cells were 25-fold higher for the adapted virus than for the parental GDVII virus, and the neurovirulence of the adapted virus in intracerebrally inoculated mice was substantially attenuated. The adapted virus showed altered cell tropism in the central nervous systems of mice, shifting from cerebral and brainstem neurons to spinal cord anterior horn cells; thus, severe poliomyelitis, but not acute encephalitis, was observed in infected mice. These data indicate that the use of HS as a coreceptor by GDVII virus facilitates cell entry and plays an important role in cell tropism and neurovirulence in vivo.

This article has been cited by other articles:

• Ryman, K. D., Gardner, C. L., Burke, C. W., Meier, K. C., Thompson, J. M., Klimstra, W. B. (2007). Heparan Sulfate Binding Can Contribute to the Neurovirulence of Neuroadapted and Nonneuroadapted Sindbis Viruses. J. Virol. 81: 3563-3573 [Abstract] [Full Text]  
• Lee, E., Wright, P. J., Davidson, A., Lobigs, M. (2006). Virulence attenuation of Dengue virus due to augmented glycosaminoglycan-binding affinity and restriction in extraneural dissemination.. J. Gen. Virol. 87: 2791-2801 [Abstract] [Full Text]  
• Fry, E. E., Newman, J. W. I., Curry, S., Najjam, S., Jackson, T., Blakemore, W., Lea, S. M., Miller, L., Burman, A., King, A. M. Q., Stuart, D. I. (2005). Structure of Foot-and-mouth disease virus serotype A1061 alone and complexed with oligosaccharide receptor: receptor conservation in the face of antigenic variation. J. Gen. Virol. 86: 1909-1920 [Abstract] [Full Text]