Zimmer Lab

Influenza A viruses

Influenza A viruses (IAV) are important pathogens that pose a threat to human and animal health. Our research is dealing with the functional aspects of the IAV envelope proteins hemagglutinin (HA), neuraminidase (NA), and matrix protein 2 (M2). The HA protein plays a crucial role in infection by mediating attachment to cellular sialoglycoconjugates, and by inducing fusion between the viral and endosomal membrane. The NA protein is a sialidase that helps progeny virus to leave the infected host cell by removing sialic acids from cell surface glycoconjugates as well as from the viral glycoproteins. In addition, IAV make use of the sialidase activity to penetrate the mucin-rich layers covering the epithelial cells of the respiratory and/or gastrointestinal tract. The M2 protein is a proton channel protein that is involved in the uncoating process after IAV has entered the cell by receptor-mediated endocytosis. M2 is also important to preserve the metastable conformation of HA in the acidic compartments of the secretory pathway.  

The envelope proteins contribute to the host and cell tropism of IAV and often contain important determinants of virulence. In addition, the IAV envelope glycoproteins are involved in virus maturation, release, and transmission, and represent important antigens that are targeted by the immune response of the host. The activity of these fascinating proteins is often linked to post-translational modifications such as oligomerization, proteolytic cleavage, and N-glycosylation. Although the interaction of the IAV envelope proteins with cellular proteins and lipids is poorly understood, it is believed that cellular proteins modulate the functions of the three IAV envelope glycoproteins.  

As an experimental approach we take advantage of reverse genetics, i.e., the generation of recombinant viruses from transfected cDNA. This approach allows us to study the impact of site-directed mutations on the replication of infectious IAV in vitro and in vivo, and it is also the basis for the development of live-attenuated IAV vaccine candidates. In addition, we are developing and evaluating novel IAV vaccines that are based on propagation-defective RNA replicon particles.