Phenotypical and functional modulation of B-lymphocytes by KSHV infection

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Herpesviruses are widely spread throughout the general population. In most cases, they only cause harmless childhood infections. In contrast to other pathogens, however, they are not eliminated from the body but rather stay in specific tissues for the rest of the life of the host. Under certain conditions, for example in immunocompromised patients, they are able to reactivate and cause life-threatening diseases. To achieve the life-long persistence in the host, herpesviruses developed a variety of measures to cope with its immune system. In contrast to other viruses, they express a large number (between approximately 70 and 170) of different proteins, most of which have not been characterized yet in terms of their function. A very large percentage of herpesviral proteins are involved in manipulating the host and its immune system. In this project, we will focus on a herpesvirus called ?Kaposi Sarcoma associated Herpesvirus? (KSHV) which causes skin tumors and lymphomas, predominantly in immuncompromised individuals as for example in AIDS patients. This herpesvirus infects cells which are very important for the immune system since they are able to produce antibodies, so-called B-lymphocytes. The infection with KSHV alters B-lymphocytes severely and has the effect that proteins which normally can be found on the surface disappear. Due to this elimination of surface proteins the infected cells can not be recognized and killed by the immune system any more. We will try to elucidate the mechanisms leading to an alteration of KSHV-infected cells and the disappearance of B-lymphocyte surface proteins. Particularly, we will search for those viral proteins which are responsible for the manipulation of B-lymphocytes. If we understand how KSHV alters infected cells, we will be able to develop new drugs which disrupt these mechanisms so that the virus can not hide from the immune system any more and is eliminated from the body. Moreover, by understanding these mechanisms we will be able to use them as tools in diseases in which a suppression of the immune system is intended, for example in auto-immune diseases, and apply them in future approaches in vaccination and gene therapy.