Immunization with structural and non-structural proteins of Theiler’s murine encephalomyelitis virus alters demyelinating disease

Abstract

Theiler’s murine encephalomyelitis virus (TMEV) causes a demyelinating disease similar to multiple sclerosis in the central nervous system (CNS) of susceptible SJL/J mice. Immune responses to TMEV contribute to viral clearance as well as to demyelination. We constructed recombinant vaccinia viruses (VV) that encode each or all of the capsid proteins (VVVP1, VVVP2, VVVP3, VVVP4, and VVall) or non-structural proteins (VVP2, VVP2P3, and VV3′P3) of the Daniels strain of TMEV. To determine the role of each of the coding regions of TMEV in vivo, we immunized SJL/J mice with each recombinant VV, with or without subsequent TMEV infection. The groups of mice were compared clinically, immunologically, and histologically. No mice immunized with any recombinant VV without subsequent TMEV infection developed demyelination. However, antibody responses to TMEV were detected in mice immunized with VVall. In addition, in some mice, VVP2 immunization induced mild meningitis. VVVP3 or VVVP4 immunization of mice prior to TMEV infection ameliorated TMEV-induced pathology or clinical signs of disease. The beneficial effect of VP4 immunization was also seen through DNA immunization with a plasmid encoding VP4 and leader prior to TMEV infection. Therefore, vaccination against not only surface capsid proteins (VVVP3 and VVall) but also non-surface capsid protein (VVVP4), and non-structural proteins (VVP2) can elicit immune responses to virus or modulate subsequent viral-induced CNS disease.

The CSF1R-Microglia Axis Has Protective Host-Specific Roles During Neurotropic Picornavirus Infection

“…Seizure activity was graded using the Racine scale: stage 1, mouth and facial movements; stage 2, head nodding; stage 3, forelimb clonus; stage 4, rearing; stage 5, rearing and falling ( 11 ). Clinical score was determined by righting reflex ( 21 ). When the proximal end of the mouse’s tail is grasped and twisted to the right and then to the left, a healthy mouse resists being turned over (score of 0).…”

Localization of gadolinium-loaded CPMV to sites of inflammation during central nervous system autoimmunity

“…Viral infections of the CNS (Theiler's murine encephalomyelitis virus, TMEV; or mouse hepatitis virus; MHV) and toxin-induced demyelination models are also applicable. [10][11][12] Each of these models allows examination of different aspects of this multifaceted disease and has served as preclinical models for development of imaging and therapeutic agents.…”