When viruses enter cells they manufacture proteins to assist in growth and replication but the body’s immune system recognizes and attacks these non-native proteins. Human Papillomavirus (HPV)(1), which causes several types of cancer but is particularly associated with cervical cancer, has developed sneaky ways of hiding in the body, but researchers at the University of Leeds have found that its ability to trick the body’s first line of defence leaves it vulnerable to counter-espionage from a second defence system.

Professor Eric Blair(2) of the University’s Faculty of Biological Sciences and Dr Graham Cook(3) from the Leeds Institute for Molecular Medicine have been specifically looking at one of the proteins produced by HPV, called E7, and have discovered that it suppresses markers on the cell surface, making infected cells much less visible to T cells, one of the body’s key defense systems.

T-cells belong to a group of white blood cells and have a special receptor on their cell surface, called the T cell receptor.

“T cells can normally tell when there are molecules in the body that shouldn't be there and activate an immune response,” says Professor Blair. “But HPV uses the E7 protein to hide from them. We've always known the virus has clever ways of defending itself, but we now know how one of its main defence mechanism works.”

However, in a twist that offers hope for the development of potential new therapies for cervical cancer, Professor Blair and Dr Cook have also discovered that this subterfuge may be the virus’s downfall.

Cells without surface protein markers are targeted by another of the body’s white blood cell armoury, Natural Killer cells - cellular assassins, which when activated, release specialised enzymes into target cells to kill them.

“Despite the body’s valiant efforts to ward off the virus, women are still contracting this awful disease, so there are clearly other mechanisms at work. We need to look at the role of the other components of the virus, to see if they prevent the Natural Killer cells from attacking,” says Professor Blair. “For example, we’ve started examining the contribution of the virus protein E6, which we believe works in partnership with E7. The recent introduction of a vaccine against HPV is an important development in the fight against cervical cancer. However, it may take many years for the vaccine to reduce the number of cases of this cancer and other approaches to eliminating tumour cells need to be discovered.”

This research was funded by Yorkshire Cancer Research, the charity’s Chief Executive, Elaine King commented: “Human Papillomavirus is extremely complex with many mechanisms affecting how it operates. However, through this research we have discovered how the E7 protein works, which is a huge step forward, and will hopefully help us to develop effective ways to combat Human Papillomavirus in the future.”

Article: Eric Blair and Graham Cook, 'Human Papillomavirus (HPV) E7 expression reduces cell-surface MHC class 1 molecules and increases susceptibility to Natural Killer (NK) cells', Oncogene, March 2008.

Notes:

1. Human Papillomaviruses are a group of DNA based viruses with over 100 known strains. Specific types of the virus, and particularly HPV 16, 18 and 31 are known to be key causes of cervical cancer. In the UK alone there are 2700 new cases of cervical cancer each year and approximately 1000 deaths. The disease often goes unnoticed for many years, with most sufferers being diagnosed between the ages of 30 and 50.

2. Professor Eric Blair is a Professor of Molecular and Cellular Biology at the University of Leeds. His principal research interests are in DNA tumour viruses, such as adenoviruses, papillomaviruses and polyomaviruses, and how these evade our immune systems.

3. Dr Graham Cook is a Senior Research Fellow at the Leeds Institute of Molecular Medicine. His main research interest is Natural Killer cells, how these are activated in the body and how they may be manipulated.