AGATE

At the Medical Faculty of the University of Erlangen-Nuremberg there exists a research unit of the Academy of Sciences and Literature in Mainz. In the long term, the research program is designed to investigate the pathogenetic role of new chronic persisting viruses in immunodeficiency and tumor diseases of the hematopoietic system and to explore new therapeutic methods. The work is carried out in cooperation between scientists of the Institute of Clinical and Molecular Virology and, as far as morphological aspects are concerned, of the Anatomical Institute II. The Institute of Virology is the National Reference Centre for AIDS-inducing retroviruses and the centre of a Collaborative Research Centre on Immunodeficiency and Lymphoproliferation.

In the foreground of the programme is a project on the molecular biology of the Kaposi sarcoma-associated human herpes virus Type 8 (HHV-8), which was discovered only a few years ago in accompanying tumours in AIDS patients. In a structural analysis of viral genomes, it was discovered that the virus contains numerous genes derived from cellular genetic material. These include coding sequences for viral cytokines and cytokine receptors, regulators of the cell cycle, anti-apoptotic proteins, anti-complementary proteins and enzymes of the nucleotide metabolism. So far, all cell-derived proteins are functional by either acting agonistically in the sense of the cellular precursor genes, exerting dominant negative functions on the corresponding signal chains or representing deregulated fragments of the precursor proteins. It is likely that the cell-derived proteins play a relevant role in the pathogenesis and tumorigenesis by HHV-8 and related n2-herpes viruses. The project will focus on the effects of viral cytokines and interferon response factors on the development and progression of AIDS-associated tumors.

Another long-term research topic in the Academy's research unit is the question of the pathogenetic role of the GB virus C, which has been known since 1995. The virus is widespread; about 15-20% of the Western European population undergo infection with this virus during their lifetime. More recent data indicate that the GB virus replicates and persists in lymphatic cells. Of particular relevance is the recent observation that the outbreak of AIDS for HIV-infected people is delayed and they have a significant survival advantage if infected with GB virus at the same time. The aim of the project is to establish procedures for reverse genetics of GB viruses to study cell tropism and mechanisms of interference with HIV and to evaluate possible strain-specific differences in the viruses. The aim is to determine the extent to which the variability of new GB viruses correlates with the interference patterns against immunodeficiency viruses.