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The search for virus in multiple sclerosis brain
D H Gilden1, M E Devlin, M P Burgoon
1Department of Neurology, University of Colorado Health Sciences Center, Denver 80262, USA.
Abstract:
Plaque-periplaque areas from MS brain tissue were explanted and propagated in tissue culture. The same in vitro techniques that successfully rescued measles virus from SSPE brain, papovavirus from PML brain, and HSV from normal human trigeminal ganglia, were applied. MS brain cells were also inoculated into chimpanzees, multiple rodent species, and embryonated hens eggs. No neurologic disease developed in experimentally infected animals, and no cytopathic effect was observed in explanted cells, or after cocultivation or fusion of MS brain cells with indicator cells. Further analysis of explanted and cocultivated cells by indirect immunofluorescence with various antiviral antisera prepared against viruses associated with post-infectious encephalomyelitis, as well as antisera to other ubiquitous viruses, failed to detect viral antigen. Finally, attempts to detect a latent enveloped virus in MS brain cells by 'superinfecting' MS brain cells in culture with vesicular stomatitis virus (VSV) did not reveal a VSV non-neutralizable fraction. Nevertheless, since oligoclonal bands (OGBs) in the CSF of patients with chronic infectious diseases of the CNS are directed against the causative agent, it is likely that OGBs in MS CSF are antibody directed against the agent or antigen that triggered disease. Although the relevant antibody may be scarce relative to irrelevant antibody in MS CSF, and only small amounts of an MS-specific antigen may be present in brain, this report provides a rationale for strategies proposed in our companion report by Owens et al which will allow detection of an MS-specific antigen or its cognate RNA in brain.
Insights
Researchers attempted to isolate a virus from multiple sclerosis (MS) brain tissue using various cell culture and animal inoculation methods. No evidence of a viral agent was found, suggesting further investigation into MS-specific antigens is warranted.
Area of Science:
- Neurovirology
- Immunology
- Cell Biology
Background:
- Multiple sclerosis (MS) is a chronic central nervous system (CNS) disease with suspected infectious or post-infectious etiologies.
- Previous studies successfully isolated viruses from other neurological diseases like Subacute Sclerosing Panencephalitis (SSPE) and Progressive Multifocal Leukoencephalopathy (PML).
Purpose of the Study:
- To investigate the presence of a viral agent in explanted brain tissue from patients with multiple sclerosis (MS).
- To apply established in vitro techniques for viral rescue and detection to MS brain cell cultures.
Main Methods:
- Explantation and propagation of MS brain tissue in cell culture.
- Inoculation of MS brain cells into various animal models (chimpanzees, rodents) and embryonated eggs.
- Cocultivation and fusion of MS cells with indicator cells.
- Indirect immunofluorescence assays using antiviral antisera.
- Superinfection assays with vesicular stomatitis virus (VSV).
Main Results:
- No neurologic disease was observed in experimentally infected animals.
- No cytopathic effect was detected in explanted or co-cultured MS cells.
- Viral antigens were not detected by immunofluorescence.
- No evidence of a latent enveloped virus was found using VSV superinfection.
Conclusions:
- Current in vitro methods failed to detect a viral agent in MS brain tissue.
- The presence of oligoclonal bands (OGBs) in MS cerebrospinal fluid (CSF) suggests an immune response to a specific agent.
- Further strategies are needed to detect potential MS-specific antigens or RNA in brain tissue.