January 13, 2022

expert reaction to study looking at Epstein-Barr virus infection and multiple sclerosis

A study published in Science looks at Epstein-Barr virus and multiple sclerosis (MS).

Prof Paul Farrell, Professor of Tumour Virology, Imperial College London, said:

“Epidemiological links between Epstein-Barr virus (EBV) and multiple sclerosis (MS) have been known for many years and this paper provides very clear confirmation of a causal role for EBV in most cases of MS. Auto-immune cross-reactions from EBV protein epitopes with cell proteins in neurons or glial cells are the most likely mechanism. Specific examples of this are mentioned in the accompanying Perspectives article and there may be several different EBV targets involved. However, current specific examples of cross-reactions only explain some of the MS cases.

“One aspect that should be considered more specifically when interpreting the data is sequence variation of the EBV. Lab assays for the immunology responses normally use the reference EBV sequence but it is now clear that there is variation in EBV in different geographic and ethnic groups, particularly in some of the proteins which are prime candidates for the cross-reacting epitopes.  This kind of geographic variation is now thought to be important in the incidence of one of the types of cancer that is also associated with EBV.  Future work should therefore include sequencing the EBV in MS cases compared to controls to determine whether this might allow explanation of more of the individual cases.  This would also be important for the development of vaccines or EBV targeted therapies which might be able to prevent or treat MS.

“An EBV vaccine would seem like the obvious solution. There is evidence that an EBV vaccine can prevent the EBV disease infectious mononucleosis (glandular fever), but no EBV vaccine candidate has yet prevented the virus from infecting and establishing long term persistence in people. So, at this stage it is not clear whether a vaccine of the types currently being developed would be able to prevent the long-term effects of EBV in MS.”

Prof Daniel Davis, Professor of Immunology, University of Manchester, said:

“By retrospectively analysing blood samples from US military personal collected between 1993 and 2013, the onset of multiple sclerosis (MS) was shown to link with a person being infected with Epstein Barr Virus. However, well over 9 in 10 people are infected with this virus worldwide, usually in childhood, and only very rarely does a problem arise. We already knew that this virus increases the risk of some cancer types, and now we know that it is also possibly a factor in multiple sclerosis, although it’s important to note for most people that have the virus, it will not cause them any problems. Crucially, we do not know why only a small fraction of people infected with this virus develop a problem. There must be other factors involved, including the inheritance of certain genes. Overall, the value of this discovery is not an immediate medical cure or treatment, but it is a major step forward in understanding MS and sets up new research working out the precise details of how this virus can sometimes lead to an auto-immune disease. There is no shortage of ideas in how this might happen in principle and hopefully the correct details will emerge soon.”

“Longitudinal analysis reveals high prevalence of Epstein-Barr Virus associated with multiple sclerosis” by Kjetil Bjornevik et al was published in Science at 19:00 UK time on Thursday 13^th January.

Declared interests

Prof Paul Farrell: “I served on an ad hoc review panel for GSK on EBV vaccines in 2019 as a one off.  I have a current grant from MRC on EBV biology including some EBV sequence variation, but the grant is not about multiple sclerosis.”

Prof Daniel Davis: “I don’t have any conflicts of interest but I am the author of three books about the immune system, most recently, The Secret Body.”