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Journal of Virology, August 2002, p. 8400-8407, Vol. 76, No. 16
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.16.8400-8407.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Heparan Sulfate Mediates Infection of High-Neurovirulence Theiler's Viruses

Honey V. Reddi and Howard L. Lipton*

Department of Neurology, Evanston Hospital, Evanston, and Departments of Neurology, Microbiology-Immunology, and Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Chicago, Illinois

Received 22 January 2002/ Accepted 30 April 2002

The mechanisms by which Theiler's murine encephalomyelitis virus (TMEV) binds and enters host cells and the molecules involved are not completely understood. In this study, we demonstrate that the high-neurovirulence TMEV GDVII virus uses the glycosaminoglycan heparan sulfate (HS) as an attachment factor that is required for efficient infection. Studies based on soluble HS-mediated inhibition of attachment and infection, removal of HS with specific enzymes, and blocking with anti-HS antibodies establish that HS mediates GDVII virus entry into mammalian cells. Data from defined proteoglycan-deficient Chinese hamster ovary mutant cells further support the role of HS in GDVII infection and indicate that the extent of sulfation is critical for infection. Neuraminidase treatment of proteoglycan-deficient cells restores permissiveness to GDVII virus, indicating that sialic acid hinders direct access of virus to the protein entry receptor. A model of the potential steps in GDVII virus entry into mammalian cells involving HS is proposed.


* Corresponding author. Mailing address: Department of Neurology, Evanston Hospital, 2650 Ridge Ave., Evanston, IL 60201. Phone: (847) 570-2168. Fax: (847) 570-1568. E-mail: hllipton{at}merle.acns.nwu.edu.


Journal of Virology, August 2002, p. 8400-8407, Vol. 76, No. 16
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.16.8400-8407.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.




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