Researchers are studying whether viruses may help trigger autoimmune diseases, including multiple sclerosis (MS), or make them worse.

During a viral infection, the immune system attacks infected cells. In some cases, viruses may also trigger the immune system to mistakenly attack healthy tissue, which can contribute to autoimmune disease. Some viruses can also stay dormant (inactive) in the body and become active again later. This may trigger more immune system activity.

Several viruses have been studied for a possible role in the development of MS. Epstein-Barr virus (EBV) has the strongest link to MS. Cytomegalovirus (CMV) and human herpes virus 6 (HHV-6) have also been studied, though their roles are still unclear.

Researchers believe MS develops from a combination of factors, including genetics and other environmental factors. Viruses are considered one possible risk factor for MS, rather than a single cause.

Epstein-Barr Virus

Epstein-Barr virus has the strongest known link to MS. EBV infection is very common, especially in children, who often have no symptoms.

When teens or young adults get EBV, many develop infectious mononucleosis (mono). Some sources estimate this happens in half or more of cases.

Having mono has been linked to a higher risk of developing MS later in life. EBV infects B cells, which are specialized immune cells that make antibodies. B cells play an important role in the development and progression of MS.

One type, called memory B cells, helps the immune system remember past infections, so it can respond quickly if the virus returns.

However, memory B cells may also carry dormant EBV, which can reactivate later. These cells may also signal other immune cells to attack myelin — the fatty tissue that surrounds and protects nerves — or other healthy tissues.

EBV and MS: Molecular Mimicry and Brain Lesions

In people with MS, EBV-infected B cells can form clusters near brain lesions. In these clusters, the B cells interact with T cells, immune cells that attack and kill infected or damaged cells.

EBV antigens, which are substances the immune system recognizes, can look a lot like myelin, the protective coating around nerves. This process is called molecular mimicry.

Because of this similarity, some T cells mistakenly attack myelin, leading to neurological damage and MS symptoms. Still, although about 90 percent to 95 percent of adults worldwide have been infected with EBV, only a small number develop MS.

Disease-Modifying Therapies and EBV

Disease-modifying therapies (DMTs) are used to treat MS by changing how the immune system works. Depending on the medication, a DMT may target B cells, T cells, or other parts of the immune system to help slow the nerve damage seen in MS.

Cytomegalovirus

Cytomegalovirus is a common viral infection that can affect people of any age. In the United States, nearly 1 in 3 children will be infected by age 5, and more than half of adults will be infected by age 40. Once a person is infected with CMV, the virus stays in their body and may reactivate later.

Most people don’t know they have CMV because their immune system keeps the virus under control. However, people with weakened immune systems may develop symptoms or more serious health issues.

CMV and MS: Mixed and Unclear Findings

The role of CMV in MS remains unclear. Studies in people have shown conflicting results, and CMV is not considered a confirmed risk factor for MS.

One multiethnic study found that previous CMV infection was linked to a lower risk of MS or its precursor, clinically isolated syndrome, in Hispanic people but not in Black or white people. This suggests the relationship between CMV and MS may differ among populations.

Other research has shown possible links between CMV and MS. In animal studies, CMV triggered immune cells to attack myelin through molecular mimicry, similar to what researchers have seen with EBV.

Some studies have also found higher levels of CMV DNA and antibodies in people with MS compared with people who don’t have MS. However, these findings have not been consistent and may reflect differences in immune system activity rather than showing that CMV causes MS.

More research is needed to better understand whether CMV plays a role in the development or progression of MS.

Human Herpesvirus 6

Human herpes virus 6 is closely related to CMV and has two forms: HHV-6A and HHV-6B. Around 95 percent of adults have been infected with HHV-6 at some point in their lives. Most people don’t have symptoms, although symptoms can occur.

HHV-6 and MS: Potential Links to Brain Inflammation

Studies have found higher levels of HHV-6 DNA in the brains of people with MS compared to people without MS. These higher levels are especially found in demyelinated plaques (lesions) in the brain.

Researchers have also found oligoclonal bands in most people with MS. These antibodies are linked to inflammation in the central nervous system (CNS). About 20 percent of these bands target HHV-6.

These findings support the theory that HHV-6 infection in the CNS may play a role in the development and progression of MS. Some research also suggests that HHV-6A may trigger MS flares, with antibody levels rising before a relapse.

Research on the John Cunningham (JC) virus, progressive multifocal leukoencephalopathy (PML), and MS may also help researchers better understand how viruses may interact with MS.

Human Endogenous Retroviruses

Human endogenous retroviruses (HERVs) are pieces of viral DNA that became part of human DNA long ago. These genetic sequences are passed down through families and make up about 8 percent of the human genome. HERVs can’t spread or create new viruses but may still trigger immune responses.

HERVs and MS: Possible Effects on the Immune System

Researchers believe HERVs may be involved in the development of MS. In 1997, researchers identified an endogenous virus they called MS-associated retrovirus (MSRV).

Higher levels of MSRV were found in the blood and cerebrospinal fluid (CSF) of people with MS compared to healthy people and people with other neurological disorders. Proteins linked to MSRV were also found in demyelinated neurons (nerve cells) in people with MS.

HERV-related proteins may trigger immune responses and nerve damage in several ways. Glial cells are found in the brain and CNS. They help support and protect nerve cells. When HERV proteins are active, glial cells may release harmful chemicals.

This may cause the immune system to attack nerve cells and other healthy tissue. It may especially affect oligodendrocytes, the cells that make myelin.

Varicella-Zoster Virus

Varicella-zoster virus (VZV), which causes chickenpox, is a common viral infection that usually affects children under age 10. After infection, the virus can remain dormant in the nervous system for decades. Zoster, or shingles, can occur later in life if the virus becomes active again.

Varicella-zoster virus is part of the herpesvirus family.

VZV and MS: Mixed Research Findings

Many people with MS have previously had chickenpox, and researchers have found VZV DNA in immune cells and CSF during MS relapses. In some cases, the viral DNA disappeared after recovery.

One study comparing 82 people with relapsing-remitting MS (RRMS) and 89 healthy people found that about 25 percent of the MS group tested positive for VZV DNA in their blood, compared with 3 percent of the healthy group. However, more than 90 percent of people in both groups had VZV antibodies, meaning they’d been exposed to the virus in the past.

Still, evidence linking VZV to MS remains inconsistent, and researchers haven’t proved that VZV causes MS. Another study of 54 people with MS found no herpesvirus DNA in blood or CSF samples, suggesting VZV may not play a role in MS.

Join the Conversation

On MyMSTeam, people share their experiences with multiple sclerosis, get advice, and find support from others who understand.

Do you have questions about how viruses may be connected to MS? Let others know in the comments below.