title: Major linear antibody epitopes and capsid proteins differentially induce protective immunity against Theiler's virus-induced demyelinating disease.
abstract: Theiler's murine encephalomyelitis virus-induced immunologically mediated demyelinating disease (TMEV-IDD) in susceptible mice provides a relevant infectious model for multiple sclerosis. Previously, we have identified six major linear antibody epitopes on the viral capsid proteins. In this study, we utilized fusion proteins containing individual capsid proteins and synthetic peptides containing the linear antibody epitopes to determine the potential role of antibody response in the course of virus-induced demyelination. Preimmunization of susceptible mice with VPI and VP2 fusion proteins, but not VP3, resulted in the protection from subsequent development of TMEV-IDD. Mice free of clinical symptoms following preimmunizations with fusion proteins displayed high levels of antibodies to the capsid proteins corresponding to the immunogens. In contrast, the level of antibodies to a particular linear epitope, A1C (VP1(262-276)), capable of efficiently neutralizing virus in vitro increased with the progression of disease. Further immunization with synthetic peptides containing individual antibody epitopes indicated that antibodies to the epitopes are differentially effective in protecting from virus-induced demyelination. Taken together, these results suggest that antibodies to only certain linear epitopes are protective and such protection may be restricted during the early stages of viral infection.
authors.affiliation: Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
authors.forename: H
authors.initials: H
authors.lastname: Yahikozawa
authors.forename: A
authors.initials: A
authors.lastname: Inoue
authors.forename: C S
authors.initials: CS
authors.lastname: Koh
authors.forename: Y K
authors.initials: YK
authors.lastname: Choe
authors.forename: B S
authors.initials: BS
authors.lastname: Kim
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D000956:Antigens, Viral / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D002213:Capsid / Q000138:chemical synthesis / Q000235:genetics / Q000276:immunology*; D036022:Capsid Proteins; D002460:Cell Line; D006224:Cricetinae; D003711:Demyelinating Diseases / Q000517:prevention & control* / Q000821:virology; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D051379:Mice; D009103:Multiple Sclerosis / Q000517:prevention & control; D011051:Poliomyelitis / Q000517:prevention & control; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D013329:Structure-Activity Relationship; D017945:Theilovirus / Q000276:immunology*; D014611:Vaccination; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D036022:Capsid Proteins; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D011993:Recombinant Fusion Proteins; C442551:VP1 protein, Theilovirus; C442556:VP2 protein, Theilovirus; C442559:VP3 protein, Theilovirus; D014765:Viral Vaccines