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Epstein-Barr Virus: What to Know, From Infection to Treatment

Epstein-Barr virus (EBV) is an ancient virus that may have coevolved with different hosts over the last 90–100 million years. EBV, also known as human herpesvirus 4 (HHV-4), belongs to the herpesvirus family and is one of the most common viruses in humans. It infects more than 90% of human population. In children, the virus usually causes no symptoms. However, in adults and teens, it can cause infectious mononucleosis (IM) and may be associated with a variety of human malignancies, including Burkitt’s lymphoma, Hodgkin’s lymphoma and non-Hodgkin’s lymphoma, post-transplant lymphoproliferative disorder (PTLD), nasopharyngeal carcinoma, as well as sporadic cancers of other tissues. It is estimated that every year, around 200,000 cancers are directly attributable to EBV.

 

EBV is highly contagious, and people contract it through contact with saliva or other bodily fluids. For example, EBV can be spread by using items, such as a toothbrush or drinking glass, that an infected person recently used. Additionally, EBV can also be transmitted through blood and semen during blood transfusions, and organ transplantations.

 

When a person has contracted the virus once, it stays there in a latent (inactive) state and can reactivate at any time. If the virus reactivates, the infected person may spread EBV to others, no matter how long it has been since the initial infection.

 

Cellular immunity plays a key role in EBV infection, and the decline of this function will lead to the activation of EBV. When the immune system detects a virus, it will dispatch cells and molecules to memorize its features so it can be fought off more swiftly in the future. Testing for EBV is recommended because symptoms of EBV infection are similar to those of several other diseases. The test detects the presence of Epstein-Barr virus antibodies. Antibodies are proteins released by the human body’s immune system in response to harmful substances called antigens.

 

There is no vaccine to protect against EBV infection. Recently, a team at Seattle’s Fred Hutchinson Cancer Research Center announced the discovery of an antibody called dubbed AMMO1, which was isolated from the blood of infected humans, and has successfully blocked EBV infection in two animal models. This preclinical evidence could pave the way to tests of a vaccine for humans.

 

Currently, there are three therapeutic approaches for EBV-associated diseases and can be broadly categorized into three groups.

  • Pharmacological Therapy

Nucleoside-analog anti-herpesvirus drugs, such as ganciclovir, acyclovir, or famciclovir, inhibit EBV in vitro. These drugs and their oral prodrugs are used for suppression of EBV reactivation during immunosuppression. Previous clinical data have shown that PTLD incidence in lung and heart-lung transplant EBV-seronegative recipients was reduced by antiviral prophylaxis with acyclovir, valacyclovir or ganciclovir.

 

  • Immunotherapy

Immunotherapeutic approaches have been studied in clinical trials for serval years, with success in some cases. Immunotherapy is effective in inducing remissions of EBV-associated post-transplant lymphoproliferative disorders (PTLD) with low-risk features. For high-risk diseases, the combination of immunotherapy and conventional therapies produced superior outcomes than conventional therapy alone. Immunotherapeutic strategies including immune checkpoint inhibitors, tumor-specific monoclonal antibodies, adoptive T-cell transfer, and cytokine immune system modulators.

 

  • Virus-Targeted Therapies

In most EBV-associated malignancies, all or nearly all of the tumor cells contain the viral genome. The most important advancement in virus-targeted therapies for EBV malignancies is undoubtedly based on artificial induction of EBV lytic-phase gene expression, followed by the exposure of tumor cells to anti-herpesvirus virus drugs.

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