Multiple sclerosis (MS) is thought to be caused by genetic factors, but environmental cues are increasingly recognized to have an impact on disease onset and development. One environmental factor suggested to play a role in MS is infectious agents, such as viruses. Now, different teams of scientists have explored the potential link between different viruses and the risk for MS.
The studies were presented today at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) 2017 Forum in Orlando, Fla., (Feb. 23-25) in a session titled “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 incidence.
Two members of this large family of viruses — MSRVenv and Syncytin-1 — 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.
Moreover, “HERV-W/MSRV was repeatedly found in MS patients (in blood, spinal fluid, and brain samples), in striking parallel with MS stages and active/remission phases, and therapy outcome. The HERV-Wenv protein is highly expressed in MS plaques, linked to the extent of active demyelination and inflammation,” researchers wrote.
Overall, the results suggest that these types of viruses may be used as biomarkers for disease progression and to assess the effects of therapeutics.
The strong evidence linking HERVs to MS prompted two ongoing clinical trials that are testing an MSRV protein (MSRVenv) as a therapeutic 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 also has been found associated with neurologic 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.
Researchers have witnessed difficulties, however, in establishing a causal association between HHV-6 and MS, due not only to the virus widespread distribution, but also to the lack of good animal models.
Jacobson believes HHV-6 is linked to MS, and his goal is to “characterize the extent and distribution of ubiquitous herpesviruses in the pathogenesis of MS.” He hypothesized 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.”
Finally, the role of another virus, the Epstein-Barr virus (EBV), was discussed 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.
In fact, the risk for developing MS is 10- and 20-fold higher in individuals infected with EBV in childhood and later in life, respectively, when compared to uninfected individuals.
Moreover, 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 have provided strong evidence of a causal relation between the two, noted Ascherio.
Overall, these three studies suggest that while data increasingly show an association between different types of viruses with MS, more studies are required to elucidate the mechanisms underlying viral infections and MS risk.