A large part of the population is living with latent herpes virus in the body. Now and then the virus can be expressed as a cold sore or genital herpes, which can be treated but not cured. When first transmitted Herpes Simplex Virus will hide in the neurons of the body for the rest of a person’s life.

Herpes can be very annoying, but the virus is without risk for most people. Some even live with herpes without knowing because it never shows. But for few people the disease can be life threatening because herpes virus can enter the brain and cause encephalitis. Every year 25-30 Danish people get encephalitis caused by herpes, and even though treatment is given almost a fourth of the patients die. Furthermore the disease can have some serious neurological complications and half of those who survive have an increased risk of developing brain damage, epilepsy, learning and concentration difficulties and depression.

Background:
In children with herpes encephalitis there has been found rare innate immune defects that can have an impact on the virus ability to enter the brain. The mechanisms of how the herpes virus enters the brain among adults have not yet been clarified, but it is assumed to be different from the mechanism among children.

This research project aims to investigate the correlation between the innate immune defects and herpes encephalitis among adults. Through a period of 5 years we have collected a cohort of patients that have been hospitalized in Department Q with encephalitis. We have done blood test on all the patients and analyzed these to seek the explanation of their lack of ability to control the infection. In our experiments the genes that are normally involved in recognition of the herpes virus have a special focus.

We have observed very rare mutations in the DNA of the patients and found that the cells show a lack of or reduced ability to activate an antiviral response against the herpes virus. We have demonstrated rare mutations in the DNA that lead to creation of defect molecules that are missing their immunological ability to defeat the virus.

The aim of the project

The aim of this research project is in two parts. If we are able to prove that people with a certain type of immune defect have an increased risk of getting herpes encephalitis, prophylactic treatment is an opportunity. This concerns families, where the mutation has been detected. If we are able to identify people with increased risk and treat them with drugs that can compensate for their lack of certain immune functions it will minimize the number of people who get the disease.

Furthermore we can learn some fundamental immunology by studying how the immune system handles herpes virus. In the long term this knowledge about the immune system could be used in the research and treatment of other immune defects or infectious diseases.