Characterization of the atypical M2 protein of bat influenza A viruses

• Forschungsstelle: IVI
• Projektnummer: 7270245

Kurzbeschreibung (Deutsch)

Durch den SNF gefördertes Projekt SNF | P3 Forschungsdatenbank | Project 189151
Das M2-Protein ist ein kleines virales Membranprotein, das im Replikationszyklus der Influenza-A-Viren vielfältige Aufgaben wahrnimmt. Die Leitfähigkeit des Proteins für Protonen spielt für die Einschleusung des viralen Genoms in die Wirtszelle eine wichtige Rolle. Für die Virusreifung ist dagegen die cytoplasmatische Region des Proteins von Bedeutung. Dieser Abschnitt des M2-Proteins interagiert mit zahlreichen zellulären Proteinen, deren Aufgabe bei der Virusreifung und -freisetzung noch weitgehend ungeklärt ist.

Abstract (Englisch)

The M2 protein of conventional influenza A virus (IAV) is a multifunctional protein, which is important for both virus entry and egress. The proton channel activity of the M2 protein, which can be inhibited by amantadine, plays a pivotal role in virus uncoating. The M2 protein also contributes to viral pathogenicity since the ion channel activity of the protein interferes with cellular homeostasis. The long cytoplasmic domain of the M2 protein interacts with viral and cellular components and this interaction might be important for virus budding and release. 
The recently identified bat IAV H17N10 and H18N11 share many features with conventional IAVs, yet their surface glycoproteins lack the canonical receptor-binding and -destroying activity of classical HA and NA, respectively. Interestingly, the primary sequences of the bat IAV M2 proteins are significantly different from the otherwise highly conserved sequences of classical  IAV M2 proteins. Our preliminary data suggest that the bat IAV M2 proteins may also functionally differ from their classical counterparts  as their proton channel activity is extremely low.
In the present project, we aim at studying the role of the M2 protein in the life cycle of bat IAV. Specifically, the project will unravel how the ion channel activity of bat IAV M2 protein is regulated and whether this activity is required for virus uncoating. A second aspect of this project is the identification and functional characterization of viral and cellular proteins that specifically bind to the long cytoplasmic domain of the M2 protein. The comparative analysis of classical and bat IAV M2 proteins will help us to understand the multiple functions of these proteins. A detailed insight into virus-host interaction may also decipher new targets for antiviral therapy of influenza disease in humans.