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Subterfuge, counter-surveillance and assassination: The body's fight with cervical cancer

March 24, 2008

The virus responsible for most cases of cervical cancer has a serious weakness which may provide hope for new treatments for the disease.

Human Papillomavirus (HPV), a virus which causes several types of cancer but is particularly associated with cervical cancer, has developed clever 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 attack from a second defence system.

When viruses enter cells, they produce proteins to assist their growth and replication, and the body's immune system is programmed to recognise and attack these non-native proteins.

Professor Eric Blair of the University's Faculty of Biological Sciences and Dr Graham Cook 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 defence systems.

"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."

University of Leeds