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Role of viruses in the etiopathogenesis of multiple sclerosis
P Sarchielli1, A Trequattrini, F Usai
1Department of Nervous and Mental Diseases, University of Perugia, Italy.
Abstract:
Epidemiological studies performed to identify the possible cause of Multiple Sclerosis (MS) suggest that an environmental agent could be involved in its etiopathogenesis. For a long time it has been hypothesized that this agent was a virus, but until now no virus specific to MS has been consistently identified. Animal models indicate that the demyelination of the central nervous system can be induced by certain families of viruses, but the implication of this in the etiopathogenesis of MS has not been clearly demonstrated. Morbilliviruses were the most studied. Research on this subject arose from the observation of the similarity between the brain lesions occurring in MS and encephalitis caused by the measles virus (Subacute Sclerosing Panencephalitis). Antimeasles, antirubella, antiherpes zoster antibodies have been found in the blood and the cerebrospinal fluid of MS patients, but the relationship between this finding and the disease is not clear. It has recently been proposed that the pathogenetic immune response in the brain of MS patients might be directed predominantly towards antigens of a DNA virus, such as JCV. This preferentially infects glial cells and causes a demyelinating syndrome in immunodeficient subjects, called Progressive Multifocal Leucoencephalopathy. The target JC viral antigens in MS could be synthesized during transient viral reactivation. A recent hypothesis is that retroviruses may intervene in the etiopathogenesis of MS. Strong interest has been taken in HTLV-I after its identification in Tropical Spastic Paraparesis, a disease with certain similarities to MS. Serologic and polymerase chain reaction findings from various authors have suggested an association between this human retrovirus and MS. However more recent data are not consistent with this. Current experiments aimed at detecting retroviral particles in long-term cultured peripheral blood monocytes and cerebrospinal fluid mononuclear cells in MS could clarify whether these cells provide a reservoir for such viruses, with a latency of many years without expression at brain level.
Insights
Environmental factors, potentially viruses, are investigated as causes of Multiple Sclerosis (MS). Research explores viral links, including morbilliviruses and human retroviruses, but definitive evidence remains elusive, necessitating further study into viral reservoirs.
Area of Science:
- Neuroimmunology
- Virology
- Epidemiology
Background:
- Multiple Sclerosis (MS) etiopathogenesis may involve an environmental agent.
- Viral involvement in MS is a long-standing hypothesis, yet no specific virus has been consistently identified.
- Animal models show viruses can induce demyelination, but direct links to MS pathogenesis are unclear.
Purpose of the Study:
- To review the evidence for viral involvement in the etiopathogenesis of Multiple Sclerosis.
- To explore potential viral candidates, including morbilliviruses, JC virus, and retroviruses.
- To discuss ongoing research into viral reservoirs in MS patients.
Main Methods:
- Review of epidemiological studies and serological findings.
- Analysis of research on viral encephalitis and demyelinating syndromes.
- Discussion of molecular techniques like polymerase chain reaction and viral culture.
Main Results:
- Antiviral antibodies (measles, rubella, herpes zoster) are found in MS patients, but their significance is uncertain.
- JC virus (JCV) is proposed as a target due to its glial cell tropism and association with Progressive Multifocal Leukoencephalopathy.
- Evidence for human T-lymphotropic virus type I (HTLV-I) in MS is inconsistent, despite initial associations.
Conclusions:
- The role of viruses in MS etiology remains inconclusive.
- Further research is needed to investigate potential viral reactivation and reservoirs, such as in monocytes and cerebrospinal fluid cells.
- Exploring novel viral candidates and their pathogenetic mechanisms is crucial for understanding MS.