DNA Vaccination against Theiler’s Murine Encephalomyelitis Virus Leads to Alterations in Demyelinating Disease

Abstract

Although the etiology of multiple sclerosis (MS) is not known, several factors play a role in this disease: genetic contributions, immunologic elements, and environmental factors. Viruses and virus infections have been associated with the initiation and/or enhancement of exacerbations in MS. Theiler’s murine encephalomyelitis virus (TMEV) infection of mice is one of the animal models used to mimic MS. In other animal model systems, DNA vaccination has been used to protect animals against a variety of virus infections. To explore the utility of DNA vaccination, we have constructed eukaryotic expression vectors encoding the TMEV capsid proteins VP1, VP2, and VP3. SJL/J mice were vaccinated intramuscularly once, twice, or three times with the different capsid protein cDNAs. This was followed by intracerebral TMEV infection to determine the effects of DNA vaccination on the course of TMEV-induced central nervous system (CNS) demyelinating disease. We found that vaccination of mice three times with cDNA encoding VP2 led to partial protection of mice from CNS demyelinating disease as determined by a decrease in clinical symptoms and histopathology. Vaccination of mice with cDNA encoding VP3 also led to a decrease in clinical symptoms. In contrast, mice vaccinated with cDNA encoding VP1 experienced a more severe disease with an earlier onset of clinical signs and enhanced histopathology compared with control mice. There was no correlation between anti-TMEV antibody titers and disease course. These results indicate that DNA immunization can modify chronic virus-induced demyelinating disease and may eventually lead to potential treatments for illnesses such as MS.

Distinct roles for IP-10/C XC L10 in three animal models, Theiler’s virus infection, EA E, and MHV infection, for multiple sclerosis: implication of differing roles for IP-10

“…A decrease in weight gain is associated with TMEV-induced disease, as is a loss of righting reflex, which is indicated by an increase in the righting reflex score. 39,40 No difference in the clinical signs between anti-IP-10-injected, NRS-injected, and no injection groups was noted, whether anti-IP-10 was given during the acute phase or the chronic phase (data not shown). Five weeks after infection, histological analysis 41,42 revealed perivascular MNC infiltration and demyelination with meningitis in the spinal cord in all groups of mice (Figure 1).…”

Protective and Detrimental Roles for Regulatory T Cells in a Viral Model for Multiple Sclerosis

“…Mice were weighed and observed daily for up to 3 months. Clinical signs of neurological disease were evaluated by measuring impairment in the righting reflex, which is a standard scoring system for motor impairment during TMEV infection . Additionally, using the righting reflex test daily does not condition the mice and improve their score .…”

Seizures following picornavirus infection

“…Motor function was measured using the righting reflex test and a rotorod (San Diego Instruments, San Diego, CA, U.S.A.). The daily righting reflex test was scored as follows: score 0, healthy mouse resists being turned over by the twisting of the proximal end of the mouse's tail to the right and left; score 1, mouse immediately rights itself on one side; score 1.5, mouse immediately rights itself on both sides; score 2, mouse rights itself in 1 to 5 s; score 3, righting takes more than 5 s; score 4, mouse unable to right itself (Rauch et al, 1987;Tolley et al, 1999;Tsunoda et al, 2001). The rotorod test was conducted on days −1, 3, 7 and 12 p.i.…”