It’s no secret that the cause of MS remains unknown. As frustrating as this may be for the thousands of Canadians affected by MS, research ensues to better understand the triggers of this complex and debilitating disease. To read about studies funded by the MS Society that focus on the cause and risk factors of MS, check out our MS Research Summaries.
Along with genetic and environmental influences, viruses have been studied to evaluate their role as a potential trigger and risk factor of MS. Several mechanisms have been proposed for how viruses may trigger MS. A commonly accepted mechanism involves the concept of molecular mimicry, which occurs when there are similarities between peptides (small molecules of linked amino acids) that are foreign and that are found within the body. In MS, many viruses have been shown to have peptides that are similar to proteins in myelin of the central nervous system. The immune system may thus believe that certain myelin cells are part of the virus, and mistakenly attack them, leading to areas of demyelination, characteristic of MS.
Click here to read more about relationship between viruses and MS from our colleagues at the National MS Society in the U.S.
Epstein-Barr virus
You may have heard of a virus called Epstein-Barr. Epstein-Barr virus (EBV) is a virus of the herpes family (human herpesvirus 4) and is best known as the cause of infectious mononucleosis, or “mono,” which occurs most often during adolescence. EBV can be spread through bodily fluids, with saliva being the most common transporter.
Many people become infected with EBV in childhood, with up to 90% of people being affected before the age of 20. However, it is often asymptomatic, meaning that there are no clinical symptoms present. This means that the infection may be a latent one, which refers to a dormant infection that can still be passed on to others but does not display any overt symptoms.
Being previously infected with EBV is what has been demonstrated as a risk factor for developing MS. A number of studies have been done in order to investigate the link between EBV and MS. I took a closer look into the evidence on this topic to get a better idea of what the research was saying. Here is what I found.
A study conducted by Dr. Strautins and fellow researchers measured antibody responses to EBV in the serum of 426 individuals with MS and 186 controls. They found that the MS group had significantly higher levels of the antibodies, thus supporting the association between EBV and MS. The body produces antibodies when it is infected with a virus or bacterium. Thus, high EBV antibody levels suggest that a large number of people with MS have been previously infected with EBV.
Another interesting study published in Neurology in 2012 took a different approach to studying the link between EBV and MS. Dr. Tzartos and colleagues analyzed post-mortem brain tissue from 10 participants who had been diagnosed with MS and 11 who were not. The researchers measures levels of pro-inflammatory cytokine interferon alpha (IFNα), a molecule that is produced quickly after EBV infection. They detected an overexpression of IFNα in the active MS lesions, and not in inactive lesions or normal brain tissue. The presence of IFNα supports the idea that latent EBV infection may have an effect on the inflammatory components of active MS lesions.
Despite the large amount of evidence pointing to a link between EBV and MS, a small number of studies have demonstrated that there is no association. One study conducted by Dr. Cocuzza and colleagues and published earlier this year in PLoS One, involved the collection of cerebrospinal fluid and blood samples from 55 individuals with relapsing-remitting MS (RRMS) and 51 with other types of neurological diseases. The samples were analyzed in order to determine if EBV DNA was present and compared the levels between the two groups. The findings from this study demonstrated an no major difference in the amount of EBV DNA between the RRMS group and the group which had other neurological diseases, thus revealing a lack of association between EBV and MS disease.
The MS Society is committed to supporting projects that look into the relationship between EBV and MS. Dr. Marc Horwitz is an MS Society-funded researcher at the University of British Columbia who is currently working on a project that is examining how EBV is able to indirectly alter and enhance the severity of MS. Dr. Horwitz’s goal is to apply his research to the development of therapeutics that will prevent the indirect effects of EBV latent infection in individuals with MS in order to stop disease progression.
HIV
The link between human immunodeficiency virus (HIV) and MS has received a lot of media attention lately. Findings from a study done by British and Australian researchers were published in the Journal of Neurology, Neurosurgery & Psychiatry last week. The study, by Dr. Julian Gold and colleagues, compared data from 21, 207 HIV-positive patients and over five million controls, using information from a large medical database. They found that HIV infection is linked to a significantly decreased risk of developing MS. The researchers hypothesized that this may be due to immunosuppression that occurs in HIV, as this may prevent the immune system from attacking the body, which is a key aspect of MS. They also suggested that medications used for HIV, known as anti-retroviral drugs, may have the potential to treat MS. A pilot study is currently underway in the UK in order to further investigate the safety of anti-retroviral treatment for relapsing-remitting MS.
Researchers argue that, if future studies confer similar results, HIV would be considered as the largest protective factor ever observed for MS.
HHV-6
Human herpesvirus 6 (HHV-6) is a set of two closely related herpes viruses, HHV-6A and HHV-6B. Like EBV, HHV-6 commonly affects people in childhood and can establish itself as a latent infection.
Many studies have studied the link between HHV-6 and MS. However, as with EBV, conflicting results have been reported. A study published in the Multiple Sclerosis Journal in 2012 followed 198 people with MS and collected serum samples to measure anti-HHV-6 as well as anti-EBV antibody levels. The researchers analyzed whether these levels were associated with relapses and disability progression. Findings indicated that the anti-HHV-6 antibodies were associated with risk of relapse in the subset of individuals diagnosed with RRMS. Results were less clear as to whether the antibody levels affected the progression of MS. The researchers concluded that levels of the specific type of antibody could act as a prognostic factor for RRMS disease course.
A systematic review conducted in 2013 examined the association between HHV-6 and MS by assessing evidence from past studies. The authors found that the majority of studies identified a correlation, as determined by higher levels of HHV-6 DNA in the serum of people with MS than in controls. They pointed out that a few of the studies found HHV-6A more frequently than HHV-6B. However, negative results were also found, and thus researchers stress the importance of further research to better understand the relationship between HHV-6 and MS.
What do you think about the link between viruses and MS? Leave a comment below!