by Aly Muhammad Ladak

For many years, the causes of human disease have slowly been changing: the development of antibiotics, improved hygiene, and widespread vaccination have lowered the burden of communicable disease on human health. Concomitantly, non-communicable diseases like cancer and cardiovascular disease are on the rise – fuelled by our sedentary lifestyles, changing diets, and other factors. Cancer and heart disease accounted for roughly 50% of all Canadian deaths in 2020, more than 10 times the impact of COVID-19.

But these two classes of disease may not be as separate as they seem. Evidence is mounting that many noncommunicable diseases may have their origins in infections (particularly viral ones). Over 60% of liver cancers occur due to Hepatitis B or C infection. 90% of cervical cancers are caused by the Human Papilloma Virus (HPV). And now it seems that most cases of multiple sclerosis (MS) may be caused by a viral infection.

The virus in question is Epstein-Barr Virus (EBV), which has a role in many diseases. EBV can cause communicable disease: it is associated with mononucleosis, and may be a factor in determining susceptibility to long covid. But it has also been shown to play a role in a variety of cancers and immune system diseases. It chiefly infects B cells, the cells in your immune system that are responsible for producing antibodies. Once you’ve been infected, the virus never truly leaves your body. It can spread to other immune cells, and its effects on infected cells can lead to cancers. These include Burkitt’s lymphoma and Hodgkin’s lymphoma – cancers which occur when the virus transforms B cells so that they grow abnormally and out of control. It can also cause diseases affecting non-immune cells, such as gastric cancer. Note, however, that these diseases certainly don’t occur in all infected individuals – a relief, given that 95% of people are infected with EBV!

It has long been suggested that EBV plays a role in MS, which involves the destruction of myelin sheaths – protective and functional coatings that surround bundles of neurons – in the brain and spinal cord. This destruction is thought to be caused by our own immune system, and viral infection is one potential trigger. EBV was suspected as the trigger because of its correlation with the condition. However, since it infects 95% of people, and since MS is so rare, it has proved difficult to assess comprehensively.
At least until now. Earlier this month, researchers at Harvard’s T.H. Chan School of Public Health published a paper showing that EBV infection increases the probability of MS by 32 times – suggesting that the virus is the main cause of MS. Studying such a common infection as a potential cause for such a rare condition proved to be a significant challenge. To overcome this challenge, the authors resorted to an unusual source of data: the US military. Twice a year, samples of serum are taken from all US soldiers and stored, meaning that the researchers were able to access over 62 million samples from 10 million soldiers. These samples could be analyzed for two key components: antibodies against EBV (which would indicate infection) and neurofilament light chain (an indicator of MS). They first used this data to determine the baseline level of EBV infection in the population (~95%). They then looked at the soldiers in the database who had been diagnosed with MS during service, and compared them to matched controls (people of the same race, age, levels of service, etc., but without MS). They found that infection with EBV increased the risk of developing MS 32-fold. To rule out the effects of general viral infections, they showed that a similar virus (cytomegalovirus) had no association with MS in these soldiers. They also looked at changes in EBV infection status and MS disease status over time, and found that MS always followed EBV infection, and often by a predictable delay. This finding suggests that the virus is a cause, and not just a correlate, of MS. This is as close as researchers can get to a causal relationship between EBV and MS, since randomized trials in this case would be unethical.

So, what does this mean for the 2.8 million people worldwide living with MS? Since only a fraction of people with EBV develop MS, other factors must be at play. However, if EBV is a key step in causing MS (as it seems to be), then stopping the virus could present an avenue to stopping the disease – regardless of the other factors involved in disease progression. According to Alberto Ascherio (the corresponding author of the study and professor of epidemiology and nutrition at Harvard), the finding “suggests that most MS cases could be prevented by stopping EBV infection, and that targeting EBV could lead to the discovery of a cure for MS.” If scientists find a way to treat infection, limit viral activity, or even develop a vaccine for EBV, this could profoundly benefit the lives of those at-risk for MS. More broadly, this finding suggests that the link between communicable and non-communicable diseases may be much deeper than previously thought, opening up new pathways of scientific understanding, and, hopefully, whole new ways to treat and prevent disease.

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