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Here's How the Epstein-Barr Virus Could Cause Some Chronic Health Conditions

Medically reviewed by Cedars-Sinai

What if just one virus was in part responsible for triggering many conditions, like multiple sclerosis, lupus, rheumatoid arthritis, cancer and maybe even mental health conditions like schizophrenia? A growing body of research suggests this could be possible. The culprit? A sneaky herpes virus 90 to 95% of the adult population has been previously exposed to called Epstein-Barr virus.

Of course, chronic illness and mental illness are not governed by one single viral infection. There are complex potential genetic, environmental and biological causes at play — but EBV keeps coming up. So what is Epstein-Barr virus (EBV) and why does it play a role in so many different chronic and mental illnesses?

What Is the Epstein-Barr Virus?

You may already know one of the infections EBV causes — mononucleosis or mono. You get “kissing disease” most often in your late teens or early 20s because it’s transmitted through saliva (i.e. kissing) and other bodily fluids. Mono leads to symptoms like a sore throat, fever and extreme fatigue. And because EBV transmits easily between people, you most likely have had it, even if you never got mono.

“By adulthood, most people have been infected with EBV,” Sarah Hochman, M.D., assistant professor of infectious disease at NYU Langone Health, told The Mighty. “It is part of the herpes virus family, a classification of related viruses (such as the virus that causes chickenpox) that cause latent infection and are never eradicated or cured from the body.”

A latent infection is one that remains hidden or stays dormant. In EBV’s case, it has discovered how to hide from your immune system. So even when it’s not causing symptoms, EBV is always there. Though it’s not 100 percent understood yet, scientists do have an idea of how EBV evades detection.

How Does EBV Affect Your Immune System?

In your immune system, a combination of cells work together to kick out invaders like bad bacteria and viruses (called antigens) to keep you healthy. Among these cells, your B cells are responsible for creating antibodies, unique proteins designed to match and mark the specific antigens of every cell your immune system decides doesn’t belong so other immune cells (bad cell-eating macrophages) can destroy them. Over time, B memory cells create a library of antibodies it can produce to prevent further infection.

To get around this detection process, researchers led by John B. Harley, M.D., Ph.D., director of the Center for Autoimmune Genomics and Etiology (CAGE) at Cincinnati Children’s Hospital, believe EBV takes over your B cells and their normal operations. This includes your genes that dictate how cells should act in your body. You have genes in every cell that control what those cells do.

Once EBV takes over your B cells, it can turn on and off your genes in unexpected ways. EBV may use small proteins called transcription factors, as Harley’s team found, to do this. Transcription factors facilitate copying information from your genes and putting it into action. They are essential to which of your genes are “switched on” or “off” and what those genes will do in your body.

EBV, therefore, can control changes in your gene expression through transcription factors that may “switch on” your risk for a chronic illness. This is why EBV is believed to be a possible environmental trigger for several conditions, especially autoimmune diseases like multiple sclerosis or lupus.

Why EBV Might Cause Autoimmune Disorders

It’s unclear why EBV seems to have an affinity for autoimmune conditions in particular. Harley had observed the connection between EBV and lupus in his past work but wanted to look closer at EBV’s impact on your genes. Harley’s 2018 study, which was published in Nature Genetics, found a particular EBV protein called EBNA2 and its transcription factors seemed to accumulate around areas in the genes connected to your risk of having an autoimmune condition.

According to this research, EBNA2 seemed to pose an increased environmental risk of turning on the genes connected to seven autoimmune conditions, including lupus, multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, type 1 diabetes, juvenile idiopathic arthritis and celiac disease. Harley’s team found EBNA2 and transcription factors occupied autoimmune risk loci — the physical location on your chromosome where your genes for autoimmune risk are located — associated with each condition. The research also showed EBNA2 occupied similar but distinct patterns around risk areas for each autoimmune disorder.

Epstein-Barr Virus and Multiple Sclerosis

The connection between EBV and MS is more established than the virus’ connection to other conditions. “MS is the most convincing autoimmune disease as far as the evidence goes,” Harley said. “It’s generally accepted that EBV is a cause of multiple sclerosis.”

Multiple sclerosis (MS) is an autoimmune condition that affects your brain, spinal cord and optic nerve. When you have MS, your immune system mistakenly thinks myelin, an insulating coating around nerve fibers in your nervous system that increases the efficiency of communications, are invaders it needs to eradicate for your safety. When the immune system attacks and damages your myelin, you may have symptoms like numbness, tingling and burning, vision problems, gait or walking difficulties, pain and weakness.

It’s still an evolving area of research, but according to James Stark, M.D., a neurologist and director of clinical trials at International Multiple Sclerosis Management Practice, one theory behind what triggers MS is directly tied to EBV. “Your immune system changes around puberty to try to become a smarter immune system instead of just fighting off everything. It really wants to focus,” Stark told The Mighty. He added:

We think maybe the immune system is almost too smart for its own good at some point if you are exposed to EBV. We think that the immune system is remembering the old infection of Epstein-Barr and is now attacking the covering of the nerves, which we call myelin. … We think the immune system thinks that coating is not supposed to be there because it’s actually mistaking it for an old infection.

Epstein-Barr Virus and Cancer Risk

EBV has been connected to other chronic conditions as well. One of these is certain types of cancer, including nasopharyngeal cancer, Hodgkin’s lymphoma and carcinoma of the stomach. However, the role of EBV in cancer risk is complex and more research is needed to better understand the link.

“EBV can increase the risk of nasopharyngeal cancer and Burkitt lymphoma,” Hochman said. “These cancers are more common in Africa and parts of Southeast Asia, so it is thought there is an environmental component interacting with EBV to increase this cancer risk.”

Epstein-Barr Virus and Schizophrenia

Scientists have also expanded their exploration into EBV into other conditions, even some mental illnesses. Work led by Faith Dickerson, Ph.D., M.P.H., a clinical psychologist and director of psychology at Sheppard Pratt Health System, for example, suggest EBV might have a role in what causes schizophrenia.

In a 2018 study published in Schizophrenia Bulletin, Dickerson and her team found higher levels of antibodies in the immune system for “one particular EBV viral protein, known as viral capsid antigen (VCA).” People with schizophrenia had 1.7 to 2.3 times greater VCA levels than those without schizophrenia that wasn’t better explained by other herpes viruses or environmental factors like smoking or prescription medications.

EBV and its connection to schizophrenia hadn’t really been studied before. But like autoimmune conditions, the exact causes of schizophrenia are not well understood. There seems to be a genetic component, but that’s only one piece of the puzzle. Based on her research, Dickerson said EBV is at least one factor to take into consideration for further research. She told The Mighty:

We do not know the cause or causes of schizophrenia. We do know that heredity plays some role, though the genes that have been identified explain only a small proportion of the risk for schizophrenia. Therefore, there are likely other factors that are involved in the etiology of the disorder, factors that come from the environment.

EBV is spread by person-to-person contact and is a common exposure in the general population — typically in late childhood or adolescence (not long before the time when schizophrenia typically has its onset). EBV can affect the [central nervous system] and can be reactivated after an initial exposure. Therefore, EBV is a good candidate to explore in terms of a possible relationship with schizophrenia.

What You Should Know

Researchers are interested in EBV because if scientists can understand what causes or contributes to chronic illness, it’s easier to find a preventative or treatment method that might reduce your risk of developing a chronic disease in the first place.

But Harley said preventative measures such as an EBV vaccine will be more difficult to develop. EBV can evade your immune system’s detection and you can likely be reexposed with the virus later in life, so developing an effective vaccine isn’t an easy task.

Developing a vaccine or other preventative treatment to stop EBV in its tracks before it triggers a chronic condition may be a tall order, but Harley said researchers will continue to investigate EBV and potential treatment options.

“We have antivirals that will inhibit the virus from making copies of itself when … it’s making viruses. But that’s not enough,” Harley said. “It looks like the autoimmune risk is coming earlier [and] we don’t have a therapy for that at the current time. We’re going to try to find one.”

Header image via Kirsty Pargeter/Getty Images

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