Although multiple sclerosis (MS) is thought to be caused by genetic factors, additional environmental elements are increasingly being recognised to have some kind of impact on the onset of the disease and its development.
Viruses are one of the many environmental factors that have been suggested to play a role in MS. In a bid to explore the potential links between different viruses and the risk of MS, scientists have conducted a number of studies.
The studies were presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) 2017 in a session called “Microbial Infections and MS”.
In the study “HERV-W endogenous retroviruses and MS”, Antonina Dolei, PHD, from Universita’ degli Studi di Sassari, in Italy, discussed the link between human endogenous retroviruses (HERVs), also known as fossil viruses, and MS. (MS. MSRVenv and Syncytin-1, which are part of a large family of viruses, were shown to have properties that lead to hyper-activation of the immune system, and have been suggested to play a role in MS development. Proteins of both viruses have been reported to cause neurodegeneration, neuroinflammation, alterations of the immune system and stress responses.
“HERV-W/MSRV was repeatedly found in MS patients’ blood, spinal fluid and brain samples, and in striking parallel with MS stages, active/remission phases and therapy outcome. The HERV-Wenv protine is highly expressive in MS plaques, linked to the extent of active demyelination and inflammation,” researchers wrote.
The results suggested that these types of virus may be used as biomarkers for disease progression and to assess the effects of therapeutics.
This evidence prompted two ongoing clinical trials that are testing a MSRV protein (MSRVenv) as a therapeutic target.(target.
In the study “Evidence Linking HHV-6 with MS,” Steve Jacobson, Chief of the Viral Immunology Section at the National Institutes of Health, National Institutes of Neurological Disorders and Stroke, discussed the potential role of the human herpes virus 6 (HHV-6) in MS.
HHV-6 has a worldwide distribution and is known for establishing lifelong latent, asymptomatic infections. The virus has been detected in normal brain tissue, but has also been found associated with neurological diseases, including MS. In fact, HHV-6 DNA has been found with increased frequency in MS lesions and outside the brain (for example in blood circulation) in periods of MS clinical exacerbation.
However, researchers have had difficulties in establishing a causal association between HHV-6 and MS because of the viruses’ widespread distribution and a lack of good animal models.
Jacobson believes HHV-6 is linked to MS, and his goal is to “characterise the extent and distribution of ubiquitous herpesviruses in the pathogenesis of MS.” He hypothesised that HHV-6 is a potential trigger for autoimmune diseases, and highlighted “that the mechanism(s) by which this virus is associated with the pathogenesis of MS will be important to define.”
The role of the Epstein-Barr virus (EBV), also was discussed in this session in a presentation titled “The relationship between Epstein Barr Virus and MS: Arguments for and against,” given by Alberto Ascherio, MD, DrPH, Professor of Epidemiology and Nutrition at the Harvard T.H. Chan School of Public Health and professor of medicine at Harvard Medical School.
“MS is extremely rare in individuals who are not infected with EBV, but it has been shown in a longitudinal study that their MS risk increases sharply following EBV infection,” Ascherio wrote.
The risk for developing MS was found to be 10 and 20 per cent higher in individuals infected with EBV in childhood and later in life, respectively, when compared to uninfected individuals.
According to Ascherio, the antibody levels against EBV (namely against the EBV nuclear antigen 1, EBNA-1) are “a strong marker of MS risk — risk of developing MS is over 30-fold higher among individuals with high anti EBNA–1 titers as compared with those with the lowest titers.”
The mechanisms linking EBV infection and MS remain largely unknown. However, epidemiological data has provided strong evidence of a causal relation between the two, noted Ascherio.
These three studies suggest that there is increasing data that suggests an association of different types of viruses with MS, but more studies are needed to fully identify the risks these viral infections post.