DZIF Research Group Host Control of Viral Latency and Reactivation (HOCOVLAR)

We are studying the T-cell response to widespread human viruses such as EBV, CMV, and HHV-6, in order to develop T-cell-based therapies to prevent and cure disease caused by these viruses.

Viruses have always been part of human life and environment. Some viruses are very widespread and, after infection, remain present in the body of healthy people for a lifetime. These viruses include Epstein-Barr virus, cytomegalovirus, and human herpesvirus 6B, three members of the herpesvirus family.

In most people, these viruses cause no or only mild disease, but they can produce severe harm in particular situations. After first infection, Epstein-Barr virus can cause an unpleasant condition with fever, malaise and fatigue called infectious mononucleosis, and some patients do not fully recover for many months. EBV also plays a role in the origin of cancers, such as some forms of Hodgkin’s disease and nasopharyngeal cancer. Cytomegalovirus can be transmitted from the mother to the unborn child, in particular when she catches the virus for the first time during pregnancy, and this can permanently damage the nervous system of the child. Human herpesvirus 6B causes the common early-childhood “three-day fever” which resolves well, but HHV-6B may also be associated with autoimmune diseases later in life.

All three viruses can give rise to severe disease in patients with an impaired immune system, for example those who have recently received stem cell transplantation to cure a cancer or an immunodeficiency. Drug treatment of disease caused by these viruses is often difficult and toxic.

In people who remain healthy, all three viruses are under successful control by the immune system, in particular by a group of white blood cells called T cells. Each T cell has a specificity for a particular small part of a certain virus. When a cell of the body is infected by the virus and starts to replicate it, a specific T cell can detect this, raise alarm, and in some cases immediately kill the infected cell to prevent further spread of the virus. Many T cells with specificities for different elements of a virus are present in infected people and appear to work together. However, it is not always clear how to identify virus-specific T cells, and often difficult to find out which of these T cells are most important in combating human disease and controlling infection.

We are studying human T-cell responses to these viruses. We are identifying the target structures (antigens and, more precisely, epitopes) within a virus that are recognized by T cells. We are developing techniques to identify, characterize, and isolate such T cells that are most likely to efficiently combat infection. This includes the study of tricks that are used by the viruses to avoid being seen by T cells, and the identification of T cells that can overcome this kind of resistance. We are testing the clinical transfer of such virus-specific T cells to patients with a defective immune system. Optimally, this kind of therapy leads to long-lasting protection, in a way that closely resembles healthy immune function.