viral membrane proteins

National Science Centre UMO-2018/30/E/NZ1/00257

keywords: membrane fusion, virus-like particle, peptide-lipid interaction

Enveloped viruses, such as e.g. influenza, are among the most significant human pathogens of the respiratory tract. Their entry into cells requires the viral envelope to fuse with the target host cell membrane. In influenza, this process is mediated by hemagglutinin which is a glycosylated trimeric transmembrane protein. Its fragment, termed as a fusion peptide (FP), inserts into the target membrane, meanwhile its C-terminal transmembrane domain (TMD) remains anchored in the viral envelope. Prior to FP exposition and insertion into the cell membrane, hemagglutinin is proteolytically cleaved and, as a response to external triggers such as pH drop, it encounters a conformational change. This extended intermediate further undergoes a number of structural rearrangements to pull the cell membrane and the viral lipid envelope closer. During this event, both FP and TMD, destabilize and dehydrate the two lipid bilayers, leading to sequential merger of the outer and inner leaflets.