What is Epstein-Barr virus?

The Epstein-Barr virus (EBV) is a type of human herpesvirus, classified under the Herpesviridae family. It was first discovered in 1964 by Epstein, Barr, and others using an improved tissue culture technique from malignant lymphoma cell cultures from African children. EBV has a spherical shape with a diameter of about 180 nm. Its nucleocapsid has icosahedral symmetry and is enveloped, which it acquires through budding from the nuclear membrane. The viral genome is a linear double-stranded DNA, approximately 172 kbp in length.

How does Epstein-Barr virus affect the body?

EBV mainly spreads through close contact via saliva or respiratory droplets, earning it the nickname “the kissing disease.” The virus replicates in the epithelial cells of the oropharynx before infecting B lymphocytes, which then enter the bloodstream and cause a systemic infection. EBV can remain dormant in lymphatic tissue throughout the body. Known for its “latent-reactivation” cycle, EBV reaches peak levels in the body about 4–6 weeks after infection and remains for life. After the primary infection, EBV stays dormant but can reactivate if the immune system weakens or during times of excessive stress.

Learn more about the Epstein-Barr Virus infection cycle：

https://www.immunopaedia.org.za/clinical-cases/infectious-diseases/an-unusual-cause-of-fulminant-hepatitis/

Symptoms of Epstein-Barr Virus

Once you're infected with EBV, symptoms can take 4 to 6 weeks to show up, but you can still pass it to others during that time. When symptoms appear, they're often mild, especially in young children, though they may not show signs of infection at all. Most symptoms tend to be like those of a cold or the flu. Teens often have more obvious symptoms of mono, including extreme fatigue.

Symptoms of Epstein-Barr virus usually include:

Fatigue

Fever

Lack of appetite

Rash

Sore throat

Swollen glands in the neck

Weak and sore muscles

Enlarged spleen and liver

After infection, young children typically show no symptoms or may have mild pharyngitis and upper respiratory infections. The main illnesses caused by EBV in children include the following:

1. Infectious Mononucleosis (IM)
The incubation period for IM is 5–15 days, usually around 9–11 days. Onset can vary from sudden to gradual, with about 40% of patients experiencing early symptoms lasting 4–5 days, such as fatigue, headache, poor appetite, nausea, loose stools, and chills. While IM has a variety of symptoms, most cases show typical signs, primarily affecting children and adolescents. Clinical features include fever, sore throat, enlargement of the liver, spleen, and lymph nodes, as well as an increase in peripheral blood lymphocytes and atypical lymphocytes. The younger the child, the less typical the symptoms may be. Diagnosis is based on clinical presentation, lab evidence of primary EBV infection, and nonspecific lab tests.

Differential Diagnosis:
It's essential to distinguish EBV infection from similar illnesses, such as cytomegalovirus, adenovirus, Toxoplasma, hepatitis viruses, HIV, and rubella virus, which can cause mononucleosis-like symptoms, as well as streptococcal pharyngitis. Atypical lymphocytes may also appear in the peripheral blood of patients with infections like cytomegalovirus, Toxoplasma, and HIV, but these are usually only present in proportions of 3%–5%. Differentiation is generally straightforward with pathogen testing and routine peripheral blood tests.

2. Chronic Active EBV Infection (CAEBV)
CAEBV is a clonal proliferative disease of cells infected with EBV, characterized by persistent active infection, typically a smoldering form with limited expression of lytic and latent antigens, and minimal virus production. CAEBV presents with a variety of symptoms, notably the persistent or recurrent mononucleosis-like symptoms such as fever, enlarged lymph nodes, splenomegaly, hepatitis, localized allergic reactions to insect bites, rash, pox-like skin blisters, diarrhea, and retinitis. Children with CAEBV show significantly elevated EBV DNA copies in peripheral blood. Currently, the most effective treatment is hematopoietic stem cell transplantation. After diagnosing CAEBV, it is important to determine the cell type infected by EBV to aid in treatment planning and prognosis assessment.

3. EBV-Associated Hemophagocytic Lymphohistiocytosis (EBV-HLH)

Hemophagocytic lymphohistiocytosis (HLH) is a severe systemic hyperinflammatory syndrome, most common in infants and young children, with cytokine storms playing a key role in its pathogenesis. In HLH, excessive inflammatory responses due to cytokine storms cause organ damage, leading to a rapid onset and progression. Without timely treatment, severe cases can lead to multiple organ failure and even death.

The main clinical features of EBV-HLH include persistent high fever, enlargement of the liver, spleen, and lymph nodes, jaundice, abnormal liver function, edema, pleural and abdominal effusions, blood cell reductions, clotting abnormalities, and central nervous system symptoms (such as seizures, coma, and encephalopathy). In severe cases, intracranial bleeding may occur.

HLH is classified into primary HLH (pHLH) and secondary HLH; EBV-HLH is a secondary form triggered by or related to EBV infection and is more common in Asian populations, especially in China and Japan. The pathophysiology of EBV-HLH involves functional impairments and abnormal activation of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells due to EBV infection, leading to excessive cytokine release and macrophage activation, causing widespread tissue damage. The prognosis for EBV-HLH is poor, with a mortality rate over 50%, and younger patients tend to have worse outcomes. In addition to routine symptomatic and supportive care, treatment options include chemo-immunotherapy and bone marrow transplantation.

EBV DNA testing serves as a valuable tool for differentiating EBV infections. Monitoring viral load in children with infectious mononucleosis (IM) is also crucial, as the disease typically lasts 2–3 weeks. If symptoms recur before the 3-month mark, early diagnosis of CAEBV or EBV-HLH may help prevent severe disease progression and aid in assessing prognosis.

For children with CAEBV or EBV-HLH, EBV DNA testing is also useful for tracking disease progression and evaluating treatment effectiveness, guiding medication use to avoid adverse effects from over-treatment. BioPerfectus will soon release the EBV test kit to support the diagnosis of EBV-related diseases.

For more on EBV-related conditions and diagnostics, stay updated with BioPerfectus

Reference:

1. https://www.webmd.com/a-to-z-guides/epstein-barr-virus
2. https://my.clevelandclinic.org/health/diseases/23469-epstein-barr-virus
3. https://www.cdc.gov/epstein-barr/php/laboratories/index.html
4. https://www.ncbi.nlm.nih.gov/books/NBK559285/
5. https://www.cdc.gov/epstein-barr/about/index.html