Epstein-Barr Virus: Dormant Global Pandemic

Epstein Barr virus was discovered only in 1964, but it turned out to be one of the most common viruses in humans. By the age of 40 years old, around 90% of people get infected with this pathogen. If the infection is so common, how it comes that we hardly aware of its existence?

Most people get infected during childhood, often in infancy as soon as maternal antibody protection disappears. Infection often proceeds asymptomatically or manifests itself in the form of infectious mononucleosis. The symptoms of this disease include fever, sore throat and swollen lymph glands and can often be taken for other common infections. This is the reason why disease usually does not get correctly diagnosed and remains unnoticed.

Although EBV infection is relatively harmless, long-term consequences can be significant

Disease is almost never fatal and symptoms tend to disappear spontaneously in several weeks. The person remains, however, infected for life since the virus becomes dormant and avoids the body’s immune response. Under certain circumstances in can be reactivated.

It seems to be associated with a number of autoimmune diseases, such as multiple sclerosis, and involved in pathogenesis of some rare cancers such as Burkitt’s lymphoma, Hodgkin’s lymphoma and nasopharyngeal carcinoma. It also represents danger for people with compromised immune system such as those with HIV. It is suspected that the infection with EBV can cause long-lasting fatigue.

Like other viral infections, EBV is involved in further complications of bacterial infections such as acute otitis media, sinusitis, and pneumonia.

Close human contact is the major way of EBV transmission from host to host

Infecting usually happens via contact with saliva of infected person (that is why the disease is sometimes called “kissing disease”). EBV in saliva originates from epithelial cells of mouth and throat. The virus cannot be transferred through the air. Infection has four to six weeks incubation period. Virus is often found in the saliva of healthy people, not only those with symptoms of infectious mononucleosis.

Initial infection with EBV occurs through the virus attacking B cells of immune system and epithelial cells in tonsils. Like other herpes viruses, EBV has so-called lytic and latent phases of infection.

Lytic phase is an initial active phase of infection when virus gets multiplied. Multiple new viral particles produced at this stageare used to infect plenty of B cells in the bodydue to the absence of host immunity in the beginning of infection. Once host develops the immune response (so-called adaptive immunity), many of these B cells enter latent (dormant) stage and only occasionally get reactivated.

Long Latent Phase Of EBV Infection Is The Key To The Success Of Pathogen

Epstein-Barr virus has three latency programs (called latency stages 1 to 3) in its life cycle. Different viral genes are turned off at each stage. Latency program 0 possibly exists when all genes are turned off. Switching off the viral genes helps the virus to stay undetected and avoid elimination by the host immune system.

In the latent (dormant) form the virus stays in the epithelial cells in the throat or in the B cells of immune system. B cells with latent virus reside mostly in the bone marrow. Virus doesn’t multiply when it is in latent stage.

The limited gene expression is an important feature of latency stage in which the virus expresses only very few proteins thus minimizing the chances of being recognized by immune system. This feature is the major reason why virus is so widespread in human population.

Reactivation of virus

To ensure the viral spread and survival, the latent virus in B cells must be awakened, re-enter lytic phase and invade new epithelial cells.

In B cells, lytic replication usually takes place only upon reactivation of dormant virus. The exact mechanism of reactivation is still unknown. It is likely that reactivation happens in response to other infections. Reactivation is often asymptomatic. Some research data suggest that reactivation of virus can avoid the attention of immune system. Reactivation in response to other infections also plays its role in avoidance of immune response. Immune system is often weakened when other infections take place.

Diagnosis of EBV infection, its treatment and prevention

The presence of EBV can be detected using antibodies against various viral proteins. None of the existing methods, unfortunately, seem to guarantee the 100% accuracy of detection. New detection techniques are being developed using different EBV specific antigens.

Taking into account how widespread the EBV is, the prevention of infection is almost impossible. Currently there are no antiviral drugs available to treat the infection. The treatment of people with infectious mononucleosis is limited to the management of symptoms. No vaccine preventing the infection is available so far, but it is being currently developed.

Effective treatment of EBV infection needs to be developed

Epstein Barr virus is one of the most successful viruses in human population infecting overwhelming majority of people worldwide. Fortunately, the manifestations of the initial disease, infectious mononucleosis, are mild and the infection rarely causes complications. The association of virus with more severe illnesses such as some autoimmune diseases and some types of cancer calls for development of effective treatment and prevention strategy against EBV.

In recent years, the EBV has found a new application as a very good vector for gene therapy. The virus can be used to bring the desirable genes to the cells of the body. The applications of EBV based vectors for cancer therapy are particularly promising.