Epstein Barr virus (EBV)

What is EBV?

The Epstein-Barr virus (EBV) is a common virus that causes glandular fever (infectious mononucleosis), usually in teenagers and young adults. It has been proposed as a possible trigger for multiple sclerosis, and is also implicated in some cancers.  

EBV, also called human herpesvirus 4, is a very widespread virus. Up to 95% of all adults have been exposed to EBV, but unless you had a case of glandular fever, you may not have noticed any symptoms.

Having had EBV infection or glandular fever doesn’t mean you will get MS. However, modern detection methods show that practically everyone with MS has previously had EBV infection.

Scientists in the US tracked people who gave repeated blood samples over several years, so they could see when they had been infected with EBV. They showed that the risk of developing MS was much higher after EBV infection had taken place.

How could EBV affect MS?

EBV can get into the central nervous system, and is present and active in the brain of most cases of MS. Since EBV infection is so widespread, what makes one person with EBV infection go on to develop MS, while another person doesn’t?

This may be where genetic susceptibility comes in, in the form of the HLA system. This is the set of individual markers that your body cells display to protect them from your own immune system. The unique collection of HLA types that you have is called your HLA haplotype.

Some HLA haplotypes appear to make you more susceptible to MS than others. It is possible that this reflects the way in which that haplotype protects against virus infection. Certain HLA haplotypes may allow EBV to spread in the body, and produce more infected cells and antibodies. EBV antibody levels have been shown to be higher in people who later go on to develop MS than those who do not.

A further possibility is that EBV can interact with our own DNA in regions where it is similar to the DNA of the Epstein-Barr virus itself. Our own genomes contain sections of DNA called HERVs (Human Endogenous Retroviruses) which seem to be viral DNA that has been incorporated into our own DNA millions of years ago. Usually HERVs are benign, but EBV infection may change the way HERVs behave, and influence the immune system in the process. One study showed that increased disease burden and speed of progression of MS was associated with increased activity in HERV regions of the genome. 

This association between EBV and the HERV regions of our DNA could suggest new directions for future MS drug research, such as anti-viral therapies that could be given after EBV infection to reduce the chances of later developing MS.

Are there vaccines for EBV?

There are several clinical trials looking at vaccines for Epstein-Barr virus. These trials are in very early stages and target different cell types involved in the immune system. One trial uses the mRNA vaccine technology used in some Covid-19 vaccines. 

If an Epstein-Barr vaccine eventually becomes available, this could reduce EBV infections. Less people may then go on to develop MS, certain cancers or glandular fever. 

Find out more

Hassani A et al
Epstein-Barr virus is present in the brain of most cases of multiple sclerosis and may engage more than just B cells.
PLoS One. 2018 Feb 2;13(2):e0192109
Full article (link is external)
Lucas RM, et al.
Epstein-Barr virus and multiple sclerosis.
Journal of Neurology, Neurosurgery and Psychiatry 2011;82(10):1142-1148.
Summary (link is external)
Munger KL, et al.
Anti-Epstein-Barr virus antibodies as serological markers of multiple sclerosis: a prospective study among United States military personnel.
Multiple Sclerosis Journal 2011;17(10):1185-1193.
Summary (link is external)
Pakpoor J, et al.
The risk of developing multiple sclerosis in individuals seronegative for Epstein-Barr virus: a meta-analysis.
Multiple Sclerosis Journal 2013;19(2):162-166.
Summary (link is external)
Dolei A
The aliens inside us: HERV-W endogenous retroviruses and multiple sclerosis
Multiple Sclerosis Journal 2018, 24(1): 42-47
Agostini S, et al.
HLA alleles modulate EBV viral load in multiple sclerosis
J Transl Med. 2018; 16: 80.
Full article (link is external)
Pender MP and Burrows SR
Epstein-Barr virus and multiple sclerosis: potential opportunities for immunotherapy.
Clin Transl Immunology. 2014 Oct 31;3(10):e27
Summary (link is external)
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