Virus persistence in an animal model of multiple sclerosis requires virion attachment to sialic acid coreceptors.
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.
Department of Neurology, Evanston Hospital, 2650 Ridge Ave., Evanston, IL 60201, USA.
A S Manoj
AS
Kumar
Honey V
HV
Reddi
Aisha Y
AY
Kung
Mauro
M
Dal Canto
Howard L
HL
Lipton
D000818:Animals; D021461:Animals, Outbred Strains; D002213:Capsid; D018188:Cardiovirus Infections / Q000503:physiopathology* / Q000821:virology; D002460:Cell Line; D006224:Cricetinae; D003588:Cytopathogenic Effect, Viral; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D051379:Mice; D009103:Multiple Sclerosis / Q000503:physiopathology* / Q000821:virology; D009154:Mutation; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism; D017945:Theilovirus / Q000235:genetics / Q000254:growth & development* / Q000472:pathogenicity; D014771:Virion / Q000378:metabolism*
D011991:Receptors, Virus; D019158:N-Acetylneuraminic Acid