Prof. Paul Klenerman studies the evolutionary relationships between persistent viruses and their human hosts. He aims to understand the role of our immune responses in determining the outcome of Hepatitis C virus infection. Hepatitis C virus infects around 200 million people worldwide and is a major cause of liver disease.
When infected by hepatitis C virus, we either clear the virus or suffer from long term infection that leads to liver damage. The critical stage happens during the first few weeks of infections. Improving the immune response against the virus could be used to protect as well as cure people from hepatitis C.
Ultimately, medical research must translate into improved treatments for patients. At the Nuffield Department of Medicine, our researchers collaborate to develop better health care, improved quality of life, and enhanced preventative measures for all patients. Our findings in the laboratory are translated into changes in clinical practice, from bench to bedside.
Q: Can you tell us about our relationship with persistent viruses?
PK: We encounter viruses throughout our life. Some of them we deal with really well and we control those beautifully, but others are trickier and they can set up long term infection. Some of the ones that set up long term infection actually do us relatively little harm, but other ones cause problems over time. This is partly because the immune response is still trying to eliminate them and there is damage in the tissue that the viruses exist in. These are the viruses we are really focusing on.
Q: Can you give us an example?
PK: The virus we are most keenly interested in is hepatitis C. This is an interesting virus because some people are able to clear the virus when they first encounter it - their immune response is really good. Whereas unfortunately the majority of people are unable to do so and the virus is able to set up long term infection and this is where the tissue damage, in this case to the liver, can occur.
Q: What is our immune response to a hepatitis C virus infection?
PK: The first few weeks of infection is the really critical time but often that is not very clinically apparent, we don't see many patients at that point. But we know what's going on is that a critical decision is being made within the immune response. Some people are able to amount a particular kind of immune response using cells called T cells, and if those cells appear to function well then the virus can be very well contained. The virus is quite tricky and unfortunately the immune response sometimes is left with a gap and the virus can sneak through. Trying to understand the differences between the responses of people who clear the virus and those who don't contain it so well has been the focus of our research.
Q: What are the most important lines of research that have developed over the past five or ten years?
PK: What we have been trying to do is pick apart the differences between the groups of people who contain hepatitis C and the majority of people who become chronically infected. We are also trying to understand in more detail what it is about the T cells and the genes that distinguish those two groups of people. We understand that the innate immune system- these are features of the immune system that happen very early - is important. But we also now know that many features of the T cells, particularly what bits of the virus they recognise, how strong those responses are, and what kind of things the cells make to contain the virus, all add up to a quality of immune response which is protective.
Q: Why does your line of research matter? Why should we put money into it?
PK: Hepatitic C is the major reason why people's liver fail in this country and the major indication for liver transplantation. If we can do anything to protect people from Hepatitis C and protect against the liver disease it causes I think it's a good thing.
Hepatitis C is a big problem globally. We think that around 170 million people in the world have got hepatitis C, and the related virus hepatitis B affects 300 million people. That is nearly 1 in 12 people in the world who have one of these viruses, which are a major cause of liver disease and liver cancer. Producing vaccines for hepatitis C and producing better treatments for hepatitis C are really important things that could affect the lives of millions of people.
Q: How does your research fit into Translational Medicine within the department?
PK: What we have tried to do is take all the findings about the different types of immune response that help clear the virus, and try and generate vaccines that produce those responses in advance so that when someone encounters hepatitis C their immune response is ready to go and can contain the virus. We have made quite a lot of progress in generating vaccines of that kind and we have put them into healthy donors. We have also tried to use that technology to improve the immune response in people who have already been infected. So we are hoping we can use our knowledge of the immunology to help us protect people from hepatitis C and even cure them from hepatitis C.