Gesundheitsforschung 2000. Analyse und Modulation der antiviralen Wirkung von Zytokinen auf HBV-Wildtyp und Varianten Schlussbericht

In line with the aims of the BMBF program, which offers support for research on infectious diseases on request and on a competitive basis, our project was geared towards answering mainly the following two questions. The first one is as to whether there are hepatitis B virus (HBV) variants which determine or influence success or failure of interferon alpha therapy. The second question to be answered was as to whether interferon alpha can induce intracellular mechanisms which result in the inhibition of or even block HBV propagation. Both questions are of great sociopolitical importance for health improvement as the currently performed therapy of chronic carriers with interferon alpha leads rarely to complete virus elimination and is rather frequently associated with severe negative side effects. Therefore, the establishment of prognostic criteria for the type of response to interferon alpha therapy, which are so far not available, would be very helpful. The results obtained so far have demonstrated that HBV populations in sera and liver of patients are often very heterogeneous and can differ drastically (see final report II.1). Therefore, we assume that the HBV populations in infected patients can influence the outcome of infection and the course of chronic infection. The change of HBV populations both during interferon therapy and under immunosuppressive conditions as well as the association of the emergence and long term persistence of specific variants with severe HBV-related liver diseases, as observed in our studies, strongly supports this assumption (see final report II.1). The elucidation of the mechanisms responsible and analysis as to whether selection of specific variants during interferon therapy are decisive factors involved in virus elimination, virus persistence or reactivation of infection/hepatitis are aims of the second funding period. In the first funding period we could also demonstrate that interferon alpha can induce antiviral mechanisms in human hepatoma cells which inhibit HBV production without having negative effects on the cell (see final report II.1). Provided it is possible to characterize these mechanisms in detail and to identify HBV variants which are resistent against these inherited cytokine-inducible antiviral strategies of cells, it should be possible to establish progonostic criteria for successful therapy of chronic HBV carriers with interferon alpha as well as to develop strategies which induce virus elimination in chronic carriers by natural antiviral mechanisms that need only to be activated. (orig.)SIGLEAvailable from TIB Hannover: DtF QN1(80,41) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Bildung und Forschung (BMBF), Bonn (Germany)DEGerman