Research Areas

Influenza A viruses are able to infect a broad range of species, such as wild birds, poultry, and many mammalian species including humans. Migratory birds are considered the natural reservoir of all influenza A viruses harboring 16 HA and 9 NA subtypes. Occasionally, influenza viruses may cross species barriers and transmit to humans leading to a variety of diseases. The aim of our studies is to identify and characterize viral and cellular factors which mediate interspecies transmission as well as enhanced pathogenesis and further transmission between mammalian hosts.

Identification and characterization of viral determinants of host adaptation, pathogenesis and transmission.

Host adaptation, pathogenesis and transmission of influenza viruses are multigenic traits determined by numerous interactions of viral and cellular factors.

Viral determinants of pathogenesis and transmission may vary depending on the virus subtype. To identify determinants involved in virus replication in the mammalian host, we are comparing influenza viruses of low and high pathogenicity in different species. Therefore, we are generating recombinant influenza viruses using the reverse genetics technique. Furthermore, we study determinants of host adaptation and pathogenesis in the mouse model while transmission properties are studied in the guinea pig model.

Identification and characterization of cellular determinants of host adaptation and pathogenesis

The viral polymerase complex plays an important role during adaptation of avian influenza A viruses to humans.

Upon interspecies transmission, the viral polymerase complex needs to be transported into the nucleus of the new host cell where viral transcription and replication takes place.

The components of the nuclear import machinery, the importin-α isoforms are divergent between birds and humans. While avian influenza viruses depend on importin-α3 for efficient viral growth in human cells, mammalian influenza viruses require importin-α7. Thus, a switch from importin-α3 to importin-α7 dependency takes place upon avian-mammalian adaptation. This allows influenza viruses to circumvent the replication inhibitory activity of importin-α3 and adapt to the replication proliferating factor importin-α7. A focus of our research is to understand these virus-host interactions and their impact on interspecies transmission and pathogenesis using a variety of cell culture models and mouse models with deleted importin-α genes.

Inhibition of viral and cellular determinants of pathogenicity using synthetic peptides

Zoonotic influenza viruses pose a potential pandemic threat to humans. The human population generally lacks a protective immune response against antigenetically novel influenza viruses transmitting from animal reservoirs.

Therefore, we are designing substrates which might inhibit influenza virus replication by directly targeting viral and cellular components required for transcription and replication. These studies will hopefully lead to novel antiviral strategies and therapeutic interventions to combat influenza virus infections.