The beginnings of EBV research in Birmingham
Epstein-Barr virus (EBV) was the first human tumour virus, discovered over sixty years ago by Sir Anthony Epstein and colleagues. It is a very common, generally harmless virus that infects people for life. However, EBV can trigger cancer in some people and when it does it is often highly aggressive. EBV causes a large range of cancers, which can occur in the head and neck, the stomach and in the blood. Some of these are more prevalent in different parts of the world, for example the blood cancer Burkitt lymphoma is the most common childhood cancer in sub-Saharan Africa.
Professor Alan Rickinson and his team played a vital role in Birmingham’s rich history of studying this virus. Following ten years working at the University of Bristol in the laboratory of Sir Anthony Epstein, the co-discoverer of the virus, Rickinson came to Birmingham in 1983 as Chair of Cancer Studies. As one of the founders of the Institute for Cancer Studies he was instrumental in overseeing its development and expansion. When Rickinson started his lab in Birmingham, researchers were just beginning to understand EBV. His team’s work revealed how the immune system normally controls EBV and how EBV can transform normal cells into cancerous ones.
The team established that following infection, EBV was able to hide in certain immune cells (B lymphocytes) and was kept in check by other immune cells (T cells). Even though EBV is usually harmless, it had two signs that it could lead to cancer. First, under laboratory conditions, it could turn normal B cells into cells that grew continuously, like cancer cells do. Second, the virus was found in the cells of two types of human tumours: Burkitt lymphoma and nasopharyngeal carcinoma.
Key discoveries from EBV research in Birmingham
Through Rickinson’s mentorship, several researchers from his team went on to develop their own internationally renowned research teams. Professor Martin Rowe and his group studied the relationship between EBV and Burkitt’s Lymphoma (BL) and showed how the virus behaves differently in cancer cells versus normal cells, producing different viral proteins. This unexpected finding, suggesting that the virus can exist in different forms, has proven to be correct in all forms of EBV cancers discovered.
Another member of Rickinson’s original team, Professor Lawrence Young, went on to study how EBV infects epithelial cells and contributes to head and neck cancer. This work led to a deeper understanding of how these proteins affect cell development and growth. He and his team, including Professor Paul Murray who also later established his own research team, showed that EBV is linked to Hodgkin lymphoma and post-transplant lymphomas, and the complex ways that different forms of the virus can lead to different types of cancer.
This last finding linked nicely with the original work of Rickinson on understanding the immune response to EBV . Dr Cliona Rooney and colleagues pursued analysis of the T cell response to EBV in healthy, virus-carrying, individuals. The team discovered how to reactivate and expand EBV-specific memory T cells, allowing them to grow them in the laboratory for the first time. In 1995, Rooney, who had by then moved to the US, established the first type of immunotherapy showing that certain EBV-positive tumours could be targeted by these T cells. This has paved the way for new treatments and deeper understanding of immune responses against EBV.
Since then, numerous researchers have conducted studies that have deepened our understanding of EBV. Birmingham researchers have shown how EBV helps cancer cells survive, how EBV is able to permanently infect different cells, how the immune response differs in several EBV-associated cancers, and discovered ways that EBV avoids being destroyed by the immune system.
The present and future of EBV research in Birmingham
Today, at the University of Birmingham, we still have world leading laboratories researching various aspects of EBV. This is built on several decades of multidisciplinary working that have been fundamental in advancing understanding of the virus and its disease potential. Drawing together findings from virology, immunology and oncology, current research is leading the way towards the discovery of new treatments for EBV-associated cancers.
Three active EBV research groups at Birmingham are led by scientists trained by Rickinson. Dr Claire Shannon-Lowe focuses on a group of rare T cell and natural killer cell cancers driven by EBV. She and her team have developed a new test to diagnose these diseases and are particularly interested in understanding why these cells are so resistant to treatment and in identifying new effective treatments. Working with colleagues locally, nationally and internationally Dr Graham Taylor developed a therapeutic vaccine to treat people with EBV cancers and is developing additional novel therapies to treat EBV infection and its cancers. Dr Heather Long’s team focuses on understanding immune control of EBV. Her recent work looks at EBV-driven lymphoma, where her team are identifying biomarkers for earlier detection and treatment.
Beyond the virus’s impact on cancer, it has become apparent that EBV is also linked to autoimmune disease, such as multiple sclerosis. New projects have begun to understand the virus’ role in these diseases. Together Shannon-Lowe, Taylor and Long are training the next generation of EBV researchers to continue the legacy of EBV research in Birmingham into the future.
