Epstein-Barr virus (EBV)

What is Epstein-Barr virus (EBV)?

Epstein-Barr virus (EBV) is a member of the genus Lymphotropic Virus in the family Herpesviridae, also known as human herpesvirus type 4 (HHV-4), and its genome is DNA. Epstein-Barr virus (EBV) has the biological property of specifically infecting humans and some primate B cells in vitro and in vivo. Epstein-Barr virus (EBV) is latent in lymphocytes for a long time, free in the cytoplasm as circular DNA, and integrated into chromosomes. The Epstein-Barr virus is a widespread herpes virus that is mainly transmitted through saliva and is infected with the virus in about 90% of adults in their lifetime. EBV infection is usually asymptomatic or causes only mild disease, but it is strongly associated with a variety of malignancies (e.g., Burkitt lymphoma, Nasopharyngeal carcinoma, and Hodgkin lymphoma) as well as autoimmune diseases (e.g., Systemic lupus erythematosus). Therefore, EBV treatment research has important clinical significance.

The morphology of Epstein-Barr virus is similar to that of other herpes viruses. Mature EBVs are spherical in shape, between 120-180 nm in size, and have about 184,000 base pairs, a total of 85 genes, encoding about 100 proteins. The basic structure can be divided into three parts: nucleoid, nucleocapsid and envelope, and the central nucleoid is a dense substance with a diameter of 45 nm, mainly containing double-stranded linear DNA, the length of which varies with different strains.

Four stages of EBV infection

Epstein-Barr virus (EBV) infection typically goes through four stages, each with its specific clinical features and patterns of viral activity:

Primary infection stage: This is the initial stage of EBV infection, which usually occurs in childhood or adolescence. At this stage, EBV mainly infects epithelial cells and B lymphocytes. Symptoms can include fever, sore throat, swollen lymph nodes, etc., and usually manifest as acute infectious mononucleosis (IM), which is due to an immune response to EBV infection

Viral incubation period: After initial infection, EBV enters the incubation period, forming a long-term latent period in the host's B cells. At this stage, the virus no longer produces noticeable symptoms, but still persists in the host. Incubation EBV has an escape mechanism for the host immune system, allowing the virus to persist in the body for a long time without being cleared.

Reactivation phase: In some cases, EBV can be reactivated from the latent state, especially if the immune system is suppressed or immunocompromised. The reactivation phase is usually accompanied by viral replication and the production of new virions.

Chronic infection and related disease stages: In the chronic infection stage, EBV may be associated with a number of long-term diseases, including certain types of cancer (e.g., Burkitt lymphoma, nasopharyngeal cancer) and immune system disorders. Chronic infection with EBV may trigger a persistent immune response and cellular abnormalities leading to a variety of clinical manifestations. These conditions often require a combination of antiviral drugs, chemotherapy and radiation therapy.

Fig.1 Epstein Barr virus latency and lytic cycle diagram. (Kerr Jonathan R, 2019)

Epstein-Barr virus-related diseases

Epstein-barr virus (EBV) is one of the most common human susceptible viruses, and its distribution areas are spread all over the world. Humans are the host of Epstein-Barr virus infection, which is mainly transmitted through saliva. Asymptomatic infection mostly occurs in young children, more than 90% of children aged 3~5 years old have been infected with Epstein-Barr virus, and more than 90% of adults have virus antibodies. Epstein-Barr virus is the causative agent of infectious mononucleosis, and Epstein-Barr virus is closely related to the occurrence of nasopharyngeal carcinoma and childhood lymphoma, and is listed as one of the human tumor viruses that may cause cancer.

Infectious mononucleosis

Infectious mononucleosis is an acute lymphoproliferative disorder that occurs after initial EBV infection in adolescence, and its clinical manifestations include fever, pharyngitis, lymphadenitis, splenomegaly, abnormal liver function, and a large number of monocytes and atypic lymphocytes in peripheral blood. After the acute phase, low-grade fever and fatigue can last up to 6 months, and the prognosis is good in normal people, and death can occur in immunocompromised patients.

Malignant lymphoma in children

Malignant lymphoma in African children, also known as Burkitt lymphoma. It is more common in children aged 5~12 years old, and occurs in the isothermal tropical areas of Central Africa, showing endemic epidemics. The most common areas are the face and palate. Children who have been severely infected with EBV before the onset of the disease can detect EBV DNA and nuclear antigen in biopsies from Burkitt lymphoma.

Nasopharyngeal cancer

Nasopharyngeal carcinoma is a common epithelial cell malignancy closely related to EBV. Biopsy of nasopharyngeal carcinoma can detect EBV DNA and nuclear antigens. It also contains higher titers of EBV-specific VCA-IgA or EA-IgA antibodies in serum.

In addition, EBV can also cause infectious mononucleosis (IM), Burkitt lymphoma (BL), nasopharyngeal carcinoma (NPC), Hodgkin's disease and other diseases.

Epstein-Barr virus treatment

Epstein-Barr virus is symptomatic with drugs that can reduce fever and pain. Some studies using antiviral drugs to treat EBV did show a reduction in the amount of virus shed in the mouth, but there was no improvement in overall symptoms. Corticosteroids are not treatable, but they may be beneficial in patients with airway compromise or autoimmune complications due to EBV infection. At present, the treatment strategy for EBV mainly focuses on three aspects: antiviral therapy, immunotherapy and vaccine development.

Antiviral therapy

In antiviral therapy, nucleoside analogues such as Acyclovir, Valacyclovir, and Ganciclovir have shown significant efficacy in inhibiting viral replication. These drugs effectively inhibit viral replication and spread by inhibiting the activity of viral DNA polymerase and blocking the synthesis of viral DNA. While these drugs have shown some success in treating EBV-induced acute infectious mononucleosis, relieving symptoms and shortening the duration of the disease, they have relatively limited efficacy in addressing EBV-related malignancies such as Burkitt lymphoma and nasopharyngeal carcinoma.

Immunotherapy

Fighting EBV infection by enhancing the patient's own immune response is a promising approach. Cell therapies such as EBV-specific T cell therapy have shown significant efficacy in EBV-associated tumors. In addition, immune checkpoint inhibitors such as PD-1 and CTLA-4 antibodies are also being studied, aiming to relieve the tumor microenvironment of T cell inhibition and improve the anti-tumor immune response.

Vaccine development

Prophylactic and therapeutic vaccines are another important strategy to block EBV infection and treat associated diseases. While there are currently no approved EBV vaccines, multiple vaccine candidates are in clinical trials, including virus-like particle-based, recombinant protein, and DNA vaccines. These vaccines are designed to induce a strong antibody response and a cellular immune response that prevents primary infection or reduces viral load.

Although some progress has been made in EBV treatment research, many challenges remain. Future research needs to further understand the mechanisms of virus-host interactions and develop more effective and safe therapeutics and vaccines to comprehensively address EBV infection and its associated diseases.

BOC Sciences provides cutting-edge, customized research reagents and services for EBV research, including high-quality antiviral compounds, antibodies, proteins, nucleic acids and cell lines, enabling researchers to further explore EBV infection mechanisms and treatments.

References

• Nowalk, Andrew, and Michael Green. Epstein-barr virus. Microbiology spectrum 4.3 (2016): 10-1128.
• Kerr, Jonathan R. Epstein-Barr virus (EBV) reactivation and therapeutic inhibitors. Journal of clinical pathology 72.10 (2019): 651-658.

※ Please kindly note that our services are for research use only.