As with all herpes viruses, after infection, the virus steadily spreads latently. The initial infection can be more serious when the immune system in the patient is compromised. Reactivation of the virus is also more likely if the immune system is compromised.
(Linda Stannard, University of Cape Town. S.A)
Fig.1. HSV-2 virus particle. Note that all herpes viruses have identical morphology and cannot be distinguished from each other under electron microscopy (Wong D 1998).
Epstein – Barr Virus (EBV)
In 1964 scientists Epstein and Barr were given the task to study cells from the recently discovered Burkitt’s lymphoma. From continuous cell lines, they found that a herpes virus was present in these cells. At this point the Epstein – Barr virus was found (Epstein-Barr virus 1999).
As we found out earlier, EBV is part of the gamma herpes subfamily of the herpes virus family. After initial infection, EBV usually lurks around the body without causing symptoms. The virus is spread from person to person through saliva, mainly by kissing. Almost everyone in the population is eventually exposed. Approximately 90% of adults show evidence of exposure. When first infected, most young children a mild flu like illness. But in adolescents the immune system overreacts producing the typical symptoms of infectious mononucleosis. After the initial infection the virus enters a latent phase (as with all herpes viruses). Instead of replicating like other viruses, EBV latently infects the body. Sometimes, the virus can be triggered by certain conditions in the host and EBV cells can become malignant. People whose immune systems are compromised by chemotherapy, transplantation or AIDS are especially at risk of developing EBV related tumours (Mentzer SJ, et al 1998).
After primary infection, the host becomes a lifelong carrier of the virus and reactivation can occur in immune compromised patients.
Epidemiology
The virus is spread through saliva, mainly through kissing; hence it has been named the kissing disease. In developed countries, most children are infected by the age of six and at this age the virus doesn’t cause severe symptoms. Children show symptoms of slight fever and sore throat. Whereas when teenagers in the age group of 14 – 20 are infected mononucleosis can develop. This is more serious, causing fever, swollen glands, fatigue and enlarged spleen. In undeveloped countries, children are infected at a much earlier stage. About 2 years old (Epstein-Barr virus 1999).
EBV can infect cells in vitro (in glass eg. Test tube) and in vivo (in life) (Griffin BE, Xue SA. 1998). Recently, virus replication has been detected in vivo in the uterine cervix, raising the possibility of sexual route for transmission of the virus which was previously unknown (Epstein-Barr virus 1999).
Pathogenesis
Once the host is infected they are a lifelong carrier of the virus. The virus spreads latently and is kept unde control by the body’s immune system.
EBV infects only the epithelial cells of the pharynx and B-lymphocytes (Kawa K. 2000). This happens when the host is infected, EBV infects the lining cells of the pharynx. As the B-cells pass the throat, they pick up the virus and it spreads throughout the body through the B-cells. Eventually it spreads to the lymph centres where it remains latent until the immune system is compromised.
EBV is associated with various diseases where it may act directly or as one of several co – factors.
Disease Association
1. Infectious mononucleosis
EBV is directly related to infectious mononucleosis (IM), which is also known as glandular fever. IM is the primary infection of EBV and in children it is very slight and no clinical treatment is required with symptoms of mild fever. In adolescents however, IM can be more serious and people infected with EBV have a 50% chance of developing infectious mononucleosis (Kawa K. 2000).
Once infected, the incubation period in the host is not known. When the infection begins to show the first signs are sore throat and swelling of the neck. The lymph glands and salivary glands also swell. Fever, sweating, chills, headaches, stiff neck and abdominal pains follow these symptoms. These can last anywhere between 2 – 6 weeks.
Enlargements of both liver and spleen are also common. They occur in about 50% of patients. When this happens it is strongly advised against physical activity to prevent serious injury. In some more serious cases the spleen can rupture and immediate surgery is required.
There is no cure. Steroids can be taken for quicker recovery and pain relievers for the throat. Otherwise only time can heal IM (Derek Wong 1998).
2. Burkitt’s lymphoma
Burkitt’s lymphoma (BL) occurs mostly in parts of malaria infested Africa and Papua New Guinea. BL is more common among children and is usually more common in males. It is a tumour mostly found in the jaw region, but can also affect the ovaries and breasts. It is a very aggressive tumour, and death can occur within 4 months of untreated cases.
BL contains an antigen called EBNA-1. (Epstein – Barr Nuclear Antigen 1). This antigen (foreign invader which stimulates the defence system) gives BL the ability to “hide” from the immune system. This means that it is very difficult to diagnose the tumour because no antibodies can be found (defence against foreign invaders; also these are what doctors look for to tell if you are infected with something) which leads to the assumptions that the host isn’t infected. This can be dangerous in cases with BL as it is a very progressive tumour (Derek Wong 1998).
Although BL is very quick to invade a host, it is very sensitive to chemotherapy and can easily be treated with chemotherapy if found in time.
3. Nasopharyngeal Carcinoma
Nasopharyngeal carcinoma (NPC) is a malignant tumour found in the nasal cavity and throat of the host. It is very rare among the worlds population but very common in Southern China where it is the more common among men and second among women. It is also found in parts of Africa, Malaysia, Alaska and Iceland. Apart from EBV there are several other co-factors leading to NPC such as consumption of salt in fish and foods containing nitrosamines (Watanabe ME. 1999).
NPC also contains the antigen EBNA-1, and is difficult to diagnose. It is also difficult to locate because of its little size. If it is untreated quickly, again death can quickly occur. It also is rapidly fatal due to the development of laryngeal and pharyngeal obstruction.
Apart from conventional cancer treatment methods, theoretically, NPC can be treated with vaccination to prevent EBV (Derek Wong 1998).
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4. Immunocompromised Patients
Transplant recipients
When patients have organ transplants, they are given drugs to suppress their immune system so the body doesn’t reject the organ. Post transplant lymphoproliferative disorder occurs when the patient contracts EBV after the transplant. This can cause various tumours as the immune system is suppressed and can’t fight of the EBV (Smets F et al 2000).
X-Linked lymphoproliferative syndrome
This syndrome only affects males with a defective gene located in the X-chromosome. This affects the body’s defences against EBV. The syndrome is responsible for half of the fatal cases of IM (Derek Wong 1998).
AIDS Patients
EBV is associated with oral leukoplakia and various lymphatic tumours. Oral leukoplakia is the manifestation of the virus on the tongue and causes lesions on the tongue. Lymphomas are the second most common malignancy among AIDS patients. Especially brain lymphoma and Burkitt’s lymphoma (Derek Wong 1998).
Diagnosis
In patients wit IM and X-Linked Lymphoproliferative Syndrome, diagnosis can be done by blood sample in which antibodies can be found. With BL and NPC histology (microscope sampling) can be used. With post transplant and AIDS patients, the antibody test can be used along with histology (Derek Wong 1998) .
Vaccination
A vaccine against EBV should be able to control both BL and NPC along with post transplant recipients. Such a vaccine should be given early in life to prevent complications such as IM. It also should not be a live vaccine as there is a chance of the carcinogenic properties of EBV is present and could cause complications. This vaccine is currently being tested in Africa (Derek Wong 1998).
Summary
The Epstein – Barr virus is probably the most successful virus worldwide in the respect that everybody is infected. It is practically impossible to stop the virus from spreading so thanks to newer technology; it is being made possible that vaccines can be produced to stop the virus from infecting the host. They are being tried in Africa and if results are positive then there is a chance that the Epstein – Barr virus can be eradicated from the population like so many other illnesses and diseases such as typhoid, polio and so on.
References
Carlson JK, Eisenstat AS, Ziporyn T (1996) The Harvard Guide to Women’s Health Harvard University Press, Cambridge, pp. 290-92.
Epstein-Barr virus (1999) University of Queensland. Revision date 29/01/01 (Access date 17/05/01)
Griffin BE, Xue SA. (1998). Epstein-Barr virus infections and their association with human Malignancies: some key questions. Ann Med 30, 249-59.
Hutchinson (1991) The Hutchinson Soft back Encyclopaedia Griffin Press Limited, Netley, pp. 390.
Kawa K. (2000). Epstein-Barr virus-associated diseases in humans. International Journal of Haematology 71, 108-17.
Mentzer SJ, Fingeroth J, Reilly JJ, Perrine SP, Faller DV. (1998). Arginine butyrate-induced susceptibility to ganciclovir in an Epstein-Barr virus associated lymphoma. Blood Cells Mol Dis 24, 114-23.
Pagano JS. (1999). Epstein-Barr virus: the first human tumour virus and its role in cancer. Proc Assoc Am Physicians 111, 573-80.
Smets F, Bodeus M, Goubau P, Reding R, Otte JB, Buts JP, Sokal EM. (2000). Characteristics of Epstein-Barr virus primary infection in paediatric liver transplant recipients. Journal of Hepatology 32,100-04.
Watanabe ME. (1999). Epstein-Barr virus: Implicated in Cancer Aetiology in China, Impetus for a Vaccine. The Scientist 13, 470-74.
Derek Wong (1998) Epstein-Barr virus. Revision date 29/05/98 (Access date 17/05/01)