Epstein-Barr Virus (EBV) is a ubiquitous human virus, belonging to the herpes family, and is often referred to as human herpesvirus 4 (HHV-4). It commonly infects individuals worldwide, with most people becoming infected at some point in their lives. Infections frequently occur without noticeable symptoms, particularly in childhood. Understanding the historical identification of such a widespread pathogen provides insight into its long-recognized presence in human populations.
The Initial Breakthrough
The Epstein-Barr Virus was discovered in March 1964 by Michael Anthony Epstein, Yvonne Barr, and Bert Achong. Their investigation began after Denis Burkitt, a surgeon, described an aggressive lymphoma common in children in central Africa. Epstein, a pathologist, became interested in a viral cause for this cancer after hearing Burkitt lecture in 1961.
Tumor samples from children with Burkitt’s lymphoma were shipped from Uganda to Epstein’s London laboratory. Epstein and Barr successfully cultured cells from these samples. Using electron microscopy, Bert Achong visualized distinct virus particles within the cultured cells. This provided the first evidence of a human virus that could cause cancer.
Unraveling its Viral Nature
After the initial observation, further work was needed to confirm the viral nature of the particles. Confirming its identity was challenging, as only a small percentage of cultured Burkitt’s lymphoma cells initially showed viral particles. Werner and Gertrude Henle at the Children’s Hospital of Philadelphia developed serological markers to detect antibodies against the new virus. Their work solidified the understanding that this was a novel human virus.
Subsequent research classified EBV as human herpesvirus 4 (HHV-4) within the Herpesviridae family, specifically the gammaherpesvirus subfamily and Lymphocryptovirus genus. EBV’s unique characteristic was its ability to immortalize human B cells in laboratory cultures. This demonstrated its capacity to induce uncontrolled cell proliferation, aiding understanding of its biological properties and disease role.
Early Disease Associations
Soon after its discovery in Burkitt’s lymphoma, researchers uncovered other conditions associated with EBV. A notable early link was established with infectious mononucleosis, or glandular fever. The Henle laboratory made this connection in 1967-1968 when a technician developed mononucleosis, and stored blood samples revealed EBV antibodies. This broadened the understanding of EBV’s role in human health beyond cancer.
Recognizing that EBV caused mononucleosis, a common and often self-limiting illness, helped explain its widespread nature. About 90% of adults globally carry the virus, often without serious symptoms. This prevalence indicated that EBV’s presence alone did not automatically lead to severe diseases like Burkitt’s lymphoma, suggesting other factors were involved. The virus’s ability to establish a lifelong latent infection, with potential reactivation, is a key biological feature.