Secrets of a cancer virus revealed
Cancer Research UK scientists lay open one of the cancer-causing secrets of the notorious Epstein-Barr Virus (EBV).
Researchers in Manchester have discovered precisely how the virus, which plays a role in several children's and adults' cancers, removes a key safeguard against uncontrolled cell division.
The findings - published in the Journal of Cell Biology1 - bring scientists closer to understanding how the virus can cause cancer in some individuals, while leaving the vast majority of those it infects unharmed. And researchers hope the advance could lead to ways of protecting people from the effects of infection or treating patients with EBV-related cancers.
Scientists at Cancer Research UK's Paterson Institute studied the effects of EBV infection on some of the key controls on cell division. In particular, they focused on a gene called p16, which acts as a set of brakes on growth and division and is one of the body's main defences against cancer.
Researchers knew that EBV was able to inactivate the p16 braking system, but they did not understand how the virus took effect. In the new study, they tested the effects of EBV in human cells called fibroblasts and discovered that a molecule produced by the virus, known as LMP1, plays a crucial role in the process.
LMP1 has two effects. Firstly, it acts as a bouncer, taking one of the key molecules that helps switch on the p16 gene and banishing it to the outskirts of the infected cell. When this molecule is excluded, p16 is switched off, leaving cells far more prone to dividing without control. Secondly, LMP1 sabotages the braking system, so that even when p16 is switched on and attempting to slam on the brakes, infected cells can keep on growing and dividing.
Cancer Research UK's Dr Eiji Hara, leading the study at the Paterson Institute, says: "Epstein-Barr Virus has a number of different cancer-promoting effects and it's important that we get to the bottom of how it works, so we may be able to find ways of treating or protecting people."
Around 90 per cent of British adults are infected with EBV. In most of us, the virus does very little harm, but in a small minority it helps to trigger cancer - being associated with Hodgkin's disease, Burkitt's lymphoma, and nasopharyngeal cancer, as well as certain rare cancers in immunosupressed transplant patients.
Working out how the virus contributes to cancer and, particularly, why it causes the disease in some people but not in others is an important area of research.
Scientists believe that LMPI may be the key to EBV's role in cancer, but they think the molecule may still have other, as yet undiscovered, effects that could also contribute to development of the disease.
Dr Hara adds: "We think we've found the virus's central cancer trigger, but we've still got a way to go in understanding exactly how the trigger works - it looks as if it may have a few more tricks up its sleeve."
Professor Robert Souhami, Director of Clinical Research for Cancer Research UK, says: "Around 15-20 per cent of all cancers are caused by viruses, so it's vital that we get a better handle on the role of viral infection.
"By teasing out the details, we should eventually put ourselves in a position where we have improved treatments for viral cancers and perhaps effective methods of prevention."
- Journal of Cell Biology162 (2): pp.173-183