Epstein-Barr Virus

Epstein-Barr virus is a member of the gamma subfamily of the large herpes virus family.  It is a double-stranded DNA virus consisting of 100 genes (4). After initial infection, all herpesviruses remain latent in the body throughout one's life.  Most people of the world are initially exposed to EBV as babies or young children and fail to develop illness.  If first exposed during adolescence or adulthood, EBV will cause infectious mononucleosis about half the time.  The symptoms of "mono," originally known as "glandular fever," include swollen lymph glands, sore throat, and fever.  In most cases EBV is not known to reactivate after clearance of the primary infection.  Instead, the host maintains a lifelong immunity to infectious mononucleosis.

EBV is presently the most prolific viral contributor to the development of human lymphomas (5).  In the rare cases of immunodeficiency, such as AIDs patients, organ transplant recipients, and genetic immune disorders, the resident EBV will reactivate in the body, causing proliferation of abnormal lymphocytes and the potential for several different lymphomas (1).  It is thought that environmental, genetic, or chemical cofactors are behind the reason that in certain geographic areas, EBV is associated with Burkitt's lymphoma (BL) and nasopharyngeal carcinoma (NPC).   Recent evidence also suggests that Hodgkin's lymphoma, T cell lymphomas, and some gastric carcinomas may be linked to EBV (2).

The virus is spread mainly through saliva.  It infects the squamous epithelial cells of the salivary gland, and B-lymphocytes.  EBV induces the proliferation of infected B-cells.  If the host immune system is unable to counteract this growth, the potential for cancer arises (3).

The host immune system responds to about 100 different antigens during the active phase of the viral cycle.  During the inactive phase the Epstein-Barr virus nuclear antigens (EBNAs 1-6) and the latent membrane proteins (LMPs 1-3) are produced.  Cytotoxic T lymphocytes (CTLs) are responsible for recognition and lysis of the viral proteins /MHC-1 complexes.  Unfortunately, in the instances of Burkitt's lymphoma and nasopharyngeal carcinoma, only one antigen appears to be produced: EBNA1.  CTLs are unable to recognize this protein, thereby providing the virus with an effective evasion strategy (3).

Producing a vaccine against Burkitt's lymphoma and nasopharyngeal carcinoma is thus challenged by the fact that it would have to either elicit a CTL response against an antigen which is usually not immunogenic, or it would have to provide 100 percent immunity from primary infection.  Phase two trials are currently underway in Australia with a recombinant peptide to EBNA3 which will hopefully confer protection by stimulating a T cell response against invading EBV (3).

References:

1. NIAID fact sheet "Epstein-Barr Virus" http://www.niaid.nih.gov/factsheets/ebv.htm
2. The Jordan Report: Accelerated development of vaccines. "Herpesvirus infections."  18-23.
http://www.niaid.nih.gov/publications/pdf/jordan.pdf
3. Australian Academy of Science.  "Kissing the Epstein-Barr virus goodbye?" http://www.science.org.au/nova/026/026key.htm
4. Niederman, J.C., Evans, A.S.  "Epstein-Barr Virus."  Viral Infections of Humans: Epidemiology and Control.  New York: Plenum, 1997, 253-283.
5. Klein, G. "EBV and B Cell Lymphomas," Herpesviruses and Immunity.  Medveczky, P.G., Friedman, H., Bendinelli, M., eds. New York: Plenum, 1998; 165-190.

*drawing of virus adapted from:
Ackerman, H.W., Berthiaume, L., Tremblay, M. Virus Life Diagrams.  New York: CRC Press, 1998; 53.
*family tree drawn from information in: Murphy, F.A., Fauquet, C.M., Bishop, D.H., et al. Virus Taxonomy: Classification and Nomenclature of Viruses. New York: Springer-Verlag, 1995; 114-126.

All drawings and text of the EBV pages are done by Julie Solomon with appropriate citations.  The site is current as of 2000 with room for future modifications.