Epstein-Barr Virus (EBV) is a type 4 herpesvirus and one of eight known viruses in the Herpesviridae family. It is primarily transmitted through saliva and other bodily fluids, earning it the nickname “kissing virus.”
EBV can affect various organs and systems in the body. For instance, it may influence the central nervous system (linked to multiple sclerosis) and the thyroid gland (as seen in Hashimoto’s thyroiditis). Additionally, EBV is associated with certain types of cancer, such as nasopharyngeal carcinoma, Burkitt lymphoma, and Hodgkin’s lymphoma.
Although many people do not recall ever having EBV, approximately 95% of adults encounter the virus at some point in their lives. Primary infection usually occurs in childhood, often asymptomatically or with mild symptoms. Infants are often protected by antibodies transferred through breast milk, provided their mothers have previously been exposed to the virus.
In adolescents and young adults, EBV may cause infectious mononucleosis, characterized by fatigue, sore throat, fever, and swollen lymph nodes. EBV has a unique ability to remain latent (dormant) in the body after the initial infection and can reactivate when the immune system is weakened. In some cases, the virus does not enter the latent phase and persists in a chronic form.
How does EBV infection differ from other viral infections?
When EBV enters the body, typically through saliva, it first infects the mucosal cells of the throat and then invades B-lymphocytes—key immune cells that produce antibodies and create immune memory. The danger of B-lymphocyte infection lies in impaired cell function, increasing the risks of chronic inflammation, autoimmune diseases, lymphomas, and reduced immunity against other infections.
Unlike other viruses, EBV exploits unique B-cell receptors, such as CD21, to transform these cells into “factories” for its replication, potentially leading to acute mononucleosis. This hijacking of the immune system underscores the distinctiveness of EBV among viral infections.
Acute EBV (Acute Infection, Mononucleosis)
As previously mentioned, Epstein-Barr virus (EBV) infection presents differently depending on age. In young children, it often occurs asymptomatically or with minimal symptoms, as their immune system responds less aggressively to the virus, preventing severe inflammation. In teenagers and young adults, the immune response is more active, particularly involving B cells, which can lead to the development of infectious mononucleosis with prominent symptoms. In older adults, the infection tends to be milder because they have usually been previously exposed to the virus and their immune system generates a more balanced response.
Infectious mononucleosis presents with the following symptoms:
- Fever – High temperature, often accompanied by chills. The fever can persist for up to 14 days, usually ranging from 38–40°C.
- Lymphadenopathy – Especially of the cervical, occipital, and axillary lymph nodes. Enlargement of the lymph nodes is considered one of the classic symptoms and is seen in most teenagers and young adults with this condition. This symptom can be mild or absent, especially in individuals with a weakened immune response.
- Sore throat – Inflammation of the throat, redness, and swelling of the tonsils, sometimes with a coating. EBV infection can also occur simultaneously with a bacterial streptococcal infection. Therefore, when sore throat symptoms are present, particularly if accompanied by high fever and lymphadenopathy, a test for streptococcus (rapid test or culture) should be performed.
- Hepatomegaly and splenomegaly – In some cases, these are associated with abdominal pain.
- General malaise – Fatigue, headaches, muscle aches, and significant weakness.
- Rash – May appear after taking certain antibiotics, which is common among many patients with EBV infection.
What Happens When the “Dormant” Virus Reactivates
After initial infection, the Epstein-Barr virus (EBV) remains in the body in a latent form. The uniqueness of this virus lies in its ability to reactivate under certain conditions, meaning it can begin to actively replicate in cells, particularly in B-lymphocytes. As a result, relapses or milder symptoms of the infection may occur. In some cases, the virus reactivates in response to a weakened immune system, triggering a new flare of inflammation in the body. The decrease in immune activity can be caused by various factors that create conditions conducive to viral reactivation:
- Stress – Physical or emotional stress can activate the virus.
- Chronic diseases – Conditions such as diabetes, HIV, and autoimmune disorders (e.g., systemic lupus erythematosus), weaken the immune system.
- Poor nutrition and lack of sleep – These factors reduce the body’s ability to fight the virus.
- Immunosuppressants – Long-term use of medications that suppress the immune system can promote viral reactivation.
Chronic Infection (Persistent EBV)
In chronic infection, the Epstein-Barr virus (EBV) remains active for an extended period, despite the immune system’s attempts to control it. Unlike the latent phase, the virus does not “hide” but continues to affect B-lymphocytes, keeping them in an active state. This contributes to prolonged inflammation in the body, which can lead to tissue and organ damage.
Chronic EBV infection is associated with an increased risk of autoimmune diseases and certain types of cancer. The ongoing inflammation caused by the active infection disrupts normal body functions and contributes to various pathological conditions.
Symptoms of chronic infection may be less pronounced than in the acute form but can last for a long time and significantly affect quality of life:
- Fatigue – One of the most common and persistent symptoms, often hindering daily activities.
- Joint and muscle pain – Patients may experience pain similar to flu or viral illness symptoms.
- Lymphadenopathy – Swelling of lymph nodes, which may be less pronounced than in acute mononucleosis but still noticeable.
- Recurring or prolonged infections – A weakened immune system may lead to frequent colds, throat infections, and other diseases.
- Sore throat and inflammation – Symptoms of throat inflammation or tonsillitis may persist or return periodically.
- Depression and psycho-emotional disorders – Chronic fatigue and pain can contribute to the development of depression, anxiety, and other psychological issues.
- Enlarged liver and spleen – In rare cases, symptoms of enlarged organs may persist, though they are often less pronounced.
- Sleep disturbances – Difficulty falling asleep or constant fatigue despite prolonged sleep.
Understanding how the Epstein-Barr virus affects the body and its potential long-term consequences is crucial. One of the most important aspects is the impact of EBV on the immune system and the possibility of triggering autoimmune processes.
What is Molecular Mimicry?
The mechanism linking viruses to autoimmune diseases is called molecular mimicry. This is a complex biological process that helps explain how viruses, including EBV, can interfere with the immune system, causing serious disturbances.
Molecular mimicry is a mechanism in which microorganisms, such as viruses, bacteria, or parasites, disguise themselves as molecules of the host organism. They synthesize proteins that are similar to those found in our body, allowing them to avoid detection by the immune system. As a result, the immune system cannot distinguish the pathogen from the body’s normal cells, enabling viruses and bacteria to “hide” and continue their activity.
Molecular mimicry can lead to many undesirable consequences. The immune system may mistakenly confuse its own cells with those of the virus and sometimes begins to attack healthy tissues, treating them as foreign. This can trigger autoimmune diseases, where the immune system starts to destroy its own cells and organs.
EBV and Autoimmune Diseases
The Epstein-Barr virus (EBV) plays a significant role in the development of several autoimmune diseases through the mechanism of molecular mimicry. This process triggers immune reactions that target not only the virus but also the tissues of the body. The consequences of this mechanism are particularly noticeable in diseases where chronic inflammation becomes a key factor in tissue damage.
Each autoimmune disease has its own characteristics, but in many cases, EBV acts as a common trigger, enhancing predisposition and provoking an immune response. Let’s take a closer look at the connection between the virus and the most studied autoimmune conditions:
- Hashimoto’s Thyroiditis is an autoimmune disease where the immune system attacks the thyroid, leading to inflammation and hypothyroidism. EBV may be one of the factors initiating this disease through molecular mimicry. Studies have shown that patients with Hashimoto’s often exhibit increased EBV activity in the blood, indicating the virus’s role in disease development.
- Systemic Lupus Erythematosus (SLE) is an autoimmune disease where the immune system attacks its own tissues and organs. EBV is considered a potential trigger for SLE. The virus can alter the body to produce substances resembling those found in human tissues. As a result, the immune system begins to attack its own cells, leading to an autoimmune reaction. Elevated levels of antibodies to EBV are frequently observed in patients with SLE, suggesting its crucial role in disease development.
- Multiple Sclerosis (MS), a neurodegenerative autoimmune disease where the immune system attacks the myelin sheaths of nerve cells, has been linked to EBV. The virus can contribute to activating the autoimmune process in the nervous system. People with MS are up to 32 times more likely to have had a previous EBV infection, indicating the virus’s role in the onset of the disease.
- Rheumatoid Arthritis (RA) is an inflammatory autoimmune disease often accompanied by pain and inflammation in the joints. EBV can act as a trigger for RA by disrupting the normal functioning of the immune system. Studies have shown that patients with RA often exhibit EBV activity, which can contribute to joint inflammation and disease progression.
- Type 1 Diabetes (T1D), an autoimmune disease in which the immune system attacks the pancreatic beta cells, may also involve EBV. Research suggests that EBV can initiate immune reactions that mistakenly target the body’s own tissues, including the pancreatic cells, contributing to the development of T1D. This happens through molecular mimicry, where the virus’s proteins are similar to those in the body, leading to an improper immune response. Increased EBV activity is commonly observed in patients with T1D, confirming its involvement in the disease’s pathogenesis. Several studies support the idea that EBV plays a role in activating autoimmune processes and the progression of diabetes in individuals with a predisposition.
- Sjögren’s Syndrome (SS) is a disease in which the immune system mistakenly attacks the salivary and lacrimal glands, leading to inflammation and reduced function. The primary symptoms include dryness of the eyes and mouth. Studies indicate that EBV may play a role in the development of Sjögren’s syndrome. The virus activates immune cells, causing inflammation in the salivary and lacrimal glands. This can lead to the immune system attacking its own cells, intensifying the autoimmune reaction. Increased EBV activity is often observed in patients with this syndrome.
How is EBV diagnosed?
The diagnosis of Epstein-Barr Virus (EBV) relies on a combination of serological tests:
- Antibodies to Viral Capsid Antigen (VCA):
- IgM: Indicates acute infection.
- IgG: Appears weeks after infection and persists for life, indicating past infection.
- Antibodies to Early Antigen (EA):
- EA-D IgG: Presence may indicate active infection or reactivation.
- Antibodies to Nuclear Antigen (EBNA):
- EBNA IgG: Develops 2–4 months post-infection and persists for life, confirming past infection.
Combination of Markers for Differentiating Stages
Using individual markers alone can be uninformative or misleading, especially in chronic infection or reactivation cases. Combining results allows for a more precise determination of the infection status.
| Stage | IgM to VCA | IgG to VCA | EA-D IgG | EBNA IgG |
|---|---|---|---|---|
| Acute Infection | (+) | (+/-) | (+/-) | (-) |
| Reactivation/Chronic | (-) | (+) | (+) | (+) |
| Past Infection | (-) | (+) | (-) | (+) |
Why is EBV rarely diagnosed?
Despite the widespread prevalence of the virus, EBV diagnosis is often overlooked in the early stages of the disease for several reasons:
- Symptoms overlap with other diseases: Acute EBV infection can present with symptoms typical of other infections, such as fever, sore throat, swollen lymph nodes, and fatigue. If these symptoms are not all prominent, the condition may be mistakenly diagnosed as another infection.
- Low diagnostic priority: EBV testing is not always done initially, especially if the symptoms are nonspecific or if the patient seeks medical help late.
- Self-limiting nature of the infection: In many cases, the virus resolves on its own without specific treatment, which reduces the motivation for early diagnosis within the healthcare system.
- Healthcare system overload: Medical attention is often focused on more serious or acute issues, such as cardiovascular diseases, oncology, or infectious pandemics. As a result, EBV is frequently ignored.
However, this attitude can lead to serious consequences. The virus often goes unnoticed until it causes complications, such as autoimmune diseases or oncological processes. When this happens, preventive measures and early diagnosis become impossible, and treatment focuses on managing already-developed complications. This leads to regret that early symptoms were not recognized in time, as timely attention could have prevented many problems, improved the quality of life for patients, and reduced the burden on the healthcare system.
Conclusion
Epstein-Barr virus (EBV) is a widely prevalent herpesvirus that infects most people during their lifetime. Its unique ability to target B-lymphocytes and remain in a latent form creates a risk for chronic inflammation, autoimmune diseases, and certain types of cancer. The symptoms of infection range from asymptomatic in children to infectious mononucleosis in adolescents and young adults.
Chronic EBV can lead to persistent fatigue, lymphadenopathy, pain, and an increased risk of diseases, including Hashimoto’s thyroiditis and multiple sclerosis. The molecular mimicry mechanism links the virus to the development of autoimmune disorders.
EBV remains an important subject of research due to its impact on health and the need for early diagnosis to prevent complications.
Here you can read the second article about therapies that may help in the treatment of EBV and other herpesviruses: Pain and Discomfort Management for EBV and Other Herpes Infections
Blood tests can be performed to detect the presence and activity of Epstein-Barr Virus (EBV) at Armin Labs, Germany.
Janos Minarovits, Gonczol E, Tibor Valyi-Nagy. Latency Strategies of Herpesviruses. Springer Science & Business Media; 2006.