Institute of Molecular Biology
Federal Research Institute for Animal Health
17493 Greifswald - Insel Riems
Phone: +49 (0) 38351 7 1237, Fax: +49 (0) 38351 7 1275
The research interests of my group comprise reassortment potential of avian strains with established human strains, live attenuated influenza vaccines, and in particular the virulence determinants of high-pathogenic avian influenza viruses (HPAIV) in avian and mammalian hosts.
Since past pandemics are due to reassortment, i.e. antigenic shift, we investigated whether contemporary low-pathogenic avian strains may transmit their hemagglutinin to human strains. Avian field strains of serotype H3 may provide their hemagglutinin gene to efficiently replicating reassortants at high frequency, indicating that contemporary low-pathogenic avian and seasonal strains are still able to generate a novel pandemic strain. Follow-up studies are to include other HA serotypes and molecular constraints of reassortment.
We generated strictly elastase-dependent virus mutants by changing the natural hemagglutinin cleavage site to another one susceptible to elastase. Their proteolytic activation and thus multi-cycle replication is prevented under natural conditions. Three proof-of-principle studies on influenza A and B viruses demonstrated that any strain can be converted into an attenuated live vaccine virus. Such prototypes will be studied in relevant influenza hosts.
HPAIV evolve from low-pathogenic precursors and carry a polybasic hemagglutinin cleavage site (HACS), the prime virulence determinant. We previously found that the introduction of a polybasic HACS into low-pathogenic avian strains did not result in high-pathogenic phenotypes. Therefore, we elucidate virulence determinants of HPAIV in addition to the essential polybasic HACS in the hemagglutinin and the other gene segments. Current findings indicate that only few adaptive changes are sufficient for evolution of low-pathogenic avian strains into HPAIV.