Molekulare Untersuchungen zur Virulenz und Wirtsadaptation von Influenza A Viren vom Subtyp H5N1 an Geflügel und Säuger Vogelgrippe Geflügelpestvirus Influenza A Virus Virulenz Pathogenität Geflügel BALB c Maus reverse Genetik Adaptation Hämagglutinin Polyerase Komplex PB2 Influenza A viruses are important pathogens of humans and animals. As the causative agent of fowl plaque highly pathogenic avian influenza viruses (HPAIV) lead to devastating losses in the poultry industry world wide. Furthermore their zoonotic character and pandemic potential especially of strains with subtype H5N1 represents a serious threat to human health. The identification of genetic markers determining virulence and host range is important for risk assessment of new emerging strains. Studying virus pathogenesis in different animal models like chickens and mice is crucial to elucidate these virulence determinants. HPAIV evolve from precursors of low virulence by the acquisition of a polybasic cleavage site motif within the hemagglutinin (HA) during the adaptation to terrestrial poultry. Therefore the ability of a low pathogenic avian influenza virus (LPAIV) of subtype H5N1 to transform into an HPAIV was investigated in the first part of this work. To this end the reverse genetic system was established for the LPAIV A Teal Germany Wv632 05 (H5N1) to generate TG05. In in vitro studies this virus was dependent on trypsin and proved to be avirulent in chicken...