Epstein-Barr virus (EBV) is a member of the herpes virus family and is a very common infective agent. It is estimated that as many as 95% of all adults have been infected by the time they reach 40 years of age, though most people are infected by the time they reach 20.
In more than half the population, EBV infections have no associated symptoms but the virus often causes infectious mononucleosis (glandular fever) with resulting fever, sore throat, and swollen lymph glands. It is rarely fatal in temperate regions but, in the tropics, it is associated with two forms cancer, Burkitt's lymphoma and nasopharyngeal carcinoma.
Once Epstein-Barr virus has infected the body, it remains semi-dormant in both the immune system and in the throat. It then retains the ability to infect new people via the saliva - hence the title, “the kissing disease”. It does not appear to be transmissable via the blood or through the air.
Epstein-Barr virus is relevant to multiple sclerosis because several studies have shown that people with MS have higher than expected levels of antibodies to the virus.
The volume of data linking EBV with MS is very impressive. As early as 1981, it was suggested that EBV might be linked to MS [Warner and Carp] and several subsequent studies have noted that the onset of MS often follows infectious mononucleosis [Operskalski at al, Lindberg et al, Marrie et al, Haahr et al and Hernan et al]. It seems that few people develop MS during or immediately after their first EBV infection, although the vast majority of people with MS have been previously infected by the virus [Munch et al].
Other studies have found higher than expected antibodies to EBV proteins, EBV serum DNA or anti-EBV killer T cells in people with MS [Levin et al, Ascherio et al, Larsen et al, Shirodaria et al and Olson et al].
These studies have found that antibodies to the viral proteins, Epstein-Barr nuclear antigens (EBNA-1 and EBNA-2), viral capsid antigen (VCA) and diffuse early antigen (EA-D), are significantly raised in people with MS. One study found that people with the highest levels of antibodies to EBNA were 33 times more likely to develop MS than people with the lowest levels [Levin et al].
Further evidence comes from another study showing that people with MS have elavated counts of anti-EBV killer T cells suggesting that these cells cross-react with both a section of protein (epitope) on the EBV and with an epitope in myelin [Olson et al].
Pertinently, two studies have found that very few people with MS have no evidence of previous EBV infections [Ascherio and Munch and Wandinger et al]. This last study also demonstrated that active EBV replication is rarely seen in people with stable MS but is correlated with MS relapses.
Direct action by Epstein-Barr virus in the central nervous system is thought to be an unlikely cause of MS because studies have failed to find any evidence of active virus in MS lesions [Morrie et al, Rodriguez Carnero et al and Hilton et al].
A possible mechanism to explain how Epstein-Barr virus is involved in multiple sclerosis is called molecular or epitopic mimicy. The idea behind this is that a small section of one of the viral proteins resembles a small section of one of the proteins in myelin. Such small sections are known as epitopes and are the means by which the immune system identifies foreign invaders for destruction.
The theory goes on that when the immune system detects the identical epitopes in myelin, it is unable to recognise that they belong to self-proteins, and attacks them. This results in the damage seen in MS lesions.
Such recognition is known as acquired immunity and involves cells known as lymphocytes. There are two main types of lymphocyte, T cells, which orchestrate the immune response, and B cells, which release antibodies. Both of these types of cell are believed to be involved in multiple sclerosis.
Usually, the immune system doesn’t allow autoreactive lymphocytes (ones that attack its own body) to develop. However, it seems that one myelin protein, Myelin Oligodendrocyte Glycoprotein (MOG), is not protected by this process [Bruno et al].
Further support for the theory comes from the discovery of T cells that are reactive to both EBV and myelin [Lang et al]. Additionally, it has been demonstrated in mice that a virus can precipitate Experimental Autoimmune Encephalomyelitis (EAE), an animal model of MS [Olson et al].
Epstein-Barr virus links:
Multiple Sclerosis and Epstein-Barr Virus
Epstein-Barr Virus Antibodies and Risk of Multiple Sclerosis
Epstein-Barr Virus and Infectious Mononucleosis
Past Viral Infection Linked to Multiple Sclerosis
High Levels Of Antibodies Against EBV In PwMS
Study Links Epstein-Barr Virus to Risk of MS
Link Between MS and Epstein-Barr Virus
T Cell Receptor Reacts With Self-Antigen and Viral Peptide in MS
Virus-Induced MS Supports Molecular Mimicry Model