The well-known adage “Herpes is forever” describes the lack of therapeutic options to conclusively cure a herpes infection. Once a herpesvirus has entered the host’s body, it stays for life, hiding in host cells in a dormant state called latency, from which it may reactivate and cause disease if the host immunity becomes impaired. Cytomegalovirus (CMV) is a member of the family of herpesviruses that causes mild or no disease in healthy individuals, but may lead to life-threatening disease upon infection or reactivation of immunocompromised hosts. This is particularly dangerous and common in bone-marrow or solid-organ transplanted people. In contrast to most other herpesviruses, CMV infects numerous cell types, including endothelial cells and bone marrow-derived cells, and therefore may cause major damage in many different organs.
Upon initial infection, the immune system typically does its job and contains the virus. It is actually quite successful in the case of CMV, since the disease course is mild or entirely absent. The virus in turn is also successful from a biological standpoint, because it establishes latency and resides in host cells for life. In the project B2, we aim to understand the initial immune reactions to CMV and their effect on latency. Type I Interferons are secreted immediately upon infection and inhibit viral growth very effectively. The role of type I Interferons during CMV latency and reactivation is less clear. In addition, the cell types that serve as sites of CMV latency are also unclear. Our study of the complex interplay between the immune system and the virus is based on virogical, cell-biology and molecular-biology methods and aims to understand the mechanism of virus silencing by the immune system at the very molecular level.