In short
Epstein-Barr virus, one of the most common viruses in the world, infects approximately 90 to 95% of adults. While most people never experience serious problems from this infection, in rare cases the virus can lead to the development of various types of lymphoma, a cancer that affects white blood cells.
What is Epstein-Barr Virus?
Epstein-Barr virus (EBV) is a member of the herpes virus family and is one of the most common human viruses. Most people become infected during childhood and may never know, due to having only mild symptoms or no symptoms at all. EBV is also known as human herpesvirus 4.
Once you get EBV, the infection stays within your body for your entire life in a dormant state where it is inactive or sleeping. The virus can reactivate and potentially cause symptoms again, regardless of when you first acquired it. The virus primarily infects B lymphocytes, which are a type of white blood cell that helps the body fight off infections.
How the Virus Spreads
The virus spreads from person to person through bodily fluids, particularly saliva. You can get EBV from an infected person by coughing or sneezing, kissing, sexual contact, sharing objects like a toothbrush or utensils, or touching items a child might have put in their mouth or drooled on.
EBV is highly contagious and can spread during the incubation period, which is the amount of time between when someone has exposure to the virus to when they experience symptoms. This period is between four to six weeks. If you have EBV, you do not have to show symptoms to pass the virus onto someone else.
The Link Between EBV and Lymphoma
EBV is linked to the development of lymphomas, which are cancers that arise from the clonal proliferation of white blood cells including B cells, T cells, and natural killer cells. EBV was originally discovered 60 years ago through its association with Burkitt lymphoma, and it is now known to be linked to a remarkably wide range of lymphoproliferative lesions and malignant lymphomas.
By EBV causing lymphomas, researchers mean that the lymphomas that have EBV genomes in the tumor cells are dependent on EBV for their development. The virus provides these tumors benefits in survival or growth or both. With each cell division, some of the EBV is lost from the division of cells. Only if the cells that retain it outgrow those that have lost it will the virus be found in growing cells.
While persistent latent EBV infection is common, the chance of any individual developing an EBV-related lymphoma is low and is influenced by ethnic, geographic, genetic, immunologic, and infectious factors.
Types of EBV-Associated Lymphomas
EBV-associated lymphomas include a diverse group of blood cancers. Some lymphomas are EBV-positive in virtually all cases, while others show varying percentages of EBV association.
Common types of EBV-associated lymphomas include:
- Burkitt lymphoma, especially the endemic form that occurs in areas of holoendemic malaria, where it is EBV-positive in virtually 100% of cases
- Hodgkin lymphoma, where around 30% of cases in North America are EBV-positive
- Diffuse large B-cell lymphoma, which is rarely EBV-related, although factors such as chronic inflammation and immunosenescence of aging are associated with EBV-positivity
- Post-transplant lymphoproliferative disorder, which particularly occurs very early post-transplant and is usually EBV-positive
- Various T-cell and NK-cell lymphomas
Who is at Higher Risk?
Immune dysfunction increases the likelihood of developing an EBV-related lymphoma. High-risk groups include patients with HIV infection, congenital immunodeficiencies, post-transplant immunosuppression, or chronic active EBV infection.
Geographic and environmental factors also play a role. For example, in areas of holoendemic malaria, primary EBV infection is followed by a period of a few years where there is a propensity to develop EBV-positive Burkitt lymphoma. In Europe, primary EBV infection that manifests as infectious mononucleosis is followed within 6 months to 10 years by increased risk of developing EBV-positive Hodgkin lymphoma.
How EBV Causes Lymphoma
The mechanisms by which EBV may promote the development of cancer are complex. The virus may directly transform B lymphocytes through expression of viral proteins. EBV infection can also lead to instability in the genetic material of cells and indirectly contribute to cancer development over many years.
There are different patterns of viral gene expression in different lymphomas, with associated implications for treatment. Only one or a few proteins may be expressed in a particular lymphoma type. This restricted protein expression allows the viral DNA to persist in cells while evading immune recognition.
For example, Burkitt lymphoma tumors typically express only a single viral protein called Epstein-Barr nuclear antigen-1, while Hodgkin lymphoma tumors express this protein as well as viral latency membrane proteins.
Treatment Approaches
The treatment of EBV-associated lymphomas depends on several factors, including the type of lymphoma, the pattern of viral gene expression, and the immune status of the patient.
EBV-related lymphomas that arise in the setting of immunosuppression may respond favorably to therapies that improve anti-viral immune function, such as reduction of immunosuppression or adoptive immunotherapy. By contrast, EBV-related tumors in immunocompetent individuals typically have more restricted viral gene expression and thus less immunogenicity.
Treatment options may include:
- Standard chemotherapy approaches
- Rituximab, a medication that targets B cells
- Adoptive T-cell therapy using EBV-specific cytotoxic T-cells
- Reduction of immunosuppression in transplant patients
- Other targeted therapies under investigation in clinical trials
The severity and complexity of EBV-associated lymphomas require a comprehensive understanding of the relationship between the virus and the immune system to develop effective treatments. Research continues to advance in this area, with new approaches being tested in clinical trials.
