Exacerbation of experimental autoimmune encephalomyelitis in rodents infected with murine gammaherpesvirus-68
James W Peacock1, Sherine F Elsawa, Cynthia C Petty
1Department of Biology, The University of North Carolina at Charlotte, Charlotte, NC 28223, USA.
Abstract:
Viral infections have long been suspected to play a role in the pathogenesis of multiple sclerosis. In the present study, two different rodent models of experimental autoimmune encephalomyelitis (EAE) were used to demonstrate the ability of murine gammaherpesvirus-68 (gammaHV-68) to exacerbate development of neurological symptoms. SJL mice received UV-inactivated gammaHV-68 or intranasalgammaHV-68, followed by immunization against proteolipid-protein peptide 139-151. Infected mice became moribund within 10 days post-immunization, whereas mice exposed to UV-inactivated gammaHV-68 recovered. In the second model, Lewis rats were exposed to UV-inactivated gammaHV-68 or to gammaHV-68, followed by passive transfer of encephalitogenic T lymphocytes specific for myelin basic protein. Consistently, infected rats had higher clinical scores, and this result was observed during acute or latent gammaHV-68 infection. It is unlikely that this gammaHV-68-induced exacerbation was due to significant viral replication within the central nervous system since nested PCR, viral plaque assays, and infectious-centers assays demonstrated no detectable virus in spinal cords or brains of infected rodents undergoing EAE. Taken together, these studies demonstrate increased clinical symptoms of EAE in rodents infected by a gammaherpesvirus that has a limited ability to invade the central nervous system.
Insights
Murine gammaherpesvirus-68 (gammaHV-68) infection exacerbates neurological symptoms in rodent models of experimental autoimmune encephalomyelitis (EAE). This exacerbation occurred despite limited viral invasion of the central nervous system.
Area of Science:
- Neuroimmunology
- Virology
- Pathogenesis of Multiple Sclerosis
Background:
- Viral infections are implicated in multiple sclerosis pathogenesis.
- Murine gammaherpesvirus-68 (gammaHV-68) is a model gammaherpesvirus.
Purpose of the Study:
- To investigate the role of gammaHV-68 in exacerbating experimental autoimmune encephalomyelitis (EAE).
- To determine if viral replication in the central nervous system (CNS) correlates with EAE exacerbation.
Main Methods:
- Two rodent models of EAE were utilized: SJL mice and Lewis rats.
- Animals were infected with gammaHV-68 or UV-inactivated gammaHV-68, followed by specific immunization or T-cell transfer protocols.
- Nested PCR, viral plaque assays, and infectious-centers assays were used to detect viral presence in the CNS.
Main Results:
- gammaHV-68 infection significantly exacerbated neurological symptoms in both EAE models.
- Infected rodents exhibited increased clinical scores during acute and latent infection.
- No detectable viral replication of gammaHV-68 was found in the spinal cords or brains of infected rodents.
Conclusions:
- gammaHV-68 infection exacerbates EAE, suggesting a role for peripheral viral effects.
- The exacerbation of EAE by gammaHV-68 is not dependent on significant viral replication within the CNS.
- These findings contribute to understanding the complex interplay between viral infections and autoimmune neurological diseases like multiple sclerosis.
