Glycoconjugate Journal

, Volume 23, Issue 1–2, pp 39–49

Differential usage of carbohydrate co-receptors influences cellular tropism of Theiler's murine encephalomyelitis virus infection of the central nervous system

  • Howard L. Lipton
  • A. S. Manoj Kumar
  • Shannon Hertzler
  • Honey V. Reddi

DOI: 10.1007/s10719-006-5436-x

Cite this article as:
Lipton, H.L., Kumar, A.S.M., Hertzler, S. et al. Glycoconj J (2006) 23: 39. doi:10.1007/s10719-006-5436-x


Theiler's murine encephalomyelitis viruses (TMEV) are ubiquitous pathogens of mice, producing either rapidly fatal encephalitis (high-neurovirulence strains) or persistent central nervous system infection and inflammatory demyelination (low-neurovirulence strains). Although a protein entry receptor has not yet been identified, carbohydrate co-receptors that effect docking and concentration of the virus on the cell surface are known for both TMEV neurovirulence groups. Low-neurovirulence TMEV use α2,3-linked N-acetylneuramic acid (sialic acid) on an N-linked glycoprotein, whereas high-neurovirulence TMEV use the proteoglycan heparan sulfate (HS) as a co-receptor. While the binding of low-neurovirulence TMEV to sialic acid can be inhibited completely, only a third of the binding of high-neurovirulence TMEV to HS is inhibitable, suggesting that high-neurovirulence strains use another co-receptor or bind directly to the putative protein entry receptor. Four amino acids on the surface (VP2 puff B) of low-neurovirulence strains make contact with sialic acid through non-covalent hydrogen bonds. Since these virus residues are conserved in all TMEV strains, the capsid conformation of this region is probably responsible for sialic acid binding. A persistence determinant that maps within the virus coat using recombinant TMEV is also conformational in nature. Low-neurovirulence virus variants that do not bind to sialic acid fail to persist in the central nervous system of mice, indicating a role for sialic acid binding in TMEV persistence. Analysis of high-neurovirulence variants that do not bind HS demonstrates that HS co-receptor usage influences neuronal tropism in brain, whereas, the HS co-receptor use is not required for the infection of spinal cord anterior horn cells associated with poliomyelitis.


Co-receptor Heparan sulfate Multiple sclerosis model Persistent infection Picornavirus Sialic acid Theiler's murine encephalomyelitis virus Viral pathogenesis 


BeAn virus

low-neurovirulence TMEV strain


baby hamster kidney fibroblast cells


central nervous system


Chinese hamster ovary cells


chondroitin sulfate A

DA virus

low-neurovirulence TMEV strain


dermatan stulfate


encephalomyocarditis virus (related Cardiovirus)



GDVII virus

high-neuroviruclence TMEV strain


heparan sulfate


keratin sulfate

Mengo virus

related Cardiovirus




N linked-specific endoglycosidase


Theiler's murine encephalomyelitis virus


UDP-galactose transporter

Copyright information

© Springer Science + Business Media, LLC 2006

Authors and Affiliations

  • Howard L. Lipton
    • 1
  • A. S. Manoj Kumar
    • 1
  • Shannon Hertzler
    • 1
  • Honey V. Reddi
    • 1
  1. 1.Department of Neurology and Microbiology-ImmunologyUniversity of Illinois at ChicagoChicago

Personalised recommendations