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Journal of Virology, August 2004, p. 8860-8867, Vol. 78, No. 16
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.16.8860-8867.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Virus Persistence in an Animal Model of Multiple Sclerosis Requires Virion Attachment to Sialic Acid Coreceptors

A. S. Manoj Kumar,1,2 Honey V. Reddi,1,2 Aisha Y. Kung,1 Mauro Dal Canto,3 and Howard L. Lipton1,2,4*

Departments of Neurology,1 Biochemistry, Molecular Biology and Cell Biology,2 Microbiology-Immunology,4 Pathology, Northwestern University, and Evanston Hospital, Evanston, Illinois3

Received 2 January 2004/ Accepted 27 April 2004

Persistent Theiler's virus infection in the central nervous system (CNS) of mice provides a highly relevant animal model for multiple sclerosis. The low-neurovirulence DA strain uses sialic acid as a coreceptor for cell binding before establishing infection. During adaptation of DA virus to growth in sialic acid-deficient cells, three amino acid substitutions (G1100D, T1081I, and T3182A) in the capsid arose, and the virus no longer used sialic acid as a coreceptor. The adapted virus retained acute CNS virulence, but its persistence in the CNS, white matter inflammation, and demyelination were largely abrogated. Infection of murine macrophage but not oligodendrocyte cultures with the adapted virus was also significantly reduced. Substitution of G1100D in an infectious DA virus cDNA clone demonstrated a major role for this mutation in loss of sialic acid binding and CNS persistence. These data indicate a direct role for sialic acid binding in Theiler's murine encephalomyelitis virus persistence and chronic demyelinating disease.

* 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 2004, p. 8860-8867, Vol. 78, No. 16
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.16.8860-8867.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.





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