Influenza virus (IV) is responsible for worldwide outbreaks of flu, causing hundreds of thousands of deaths every year. This virus is encapsulated by a lipid membrane containing two surface glycoproteins: hemagglutinin (HA) and neuroaminidase.
HA plays a key role in infection, being responsible for binding the host receptors, and promoting the fusion of the viral and host membranes. This protein is a homotrimer and each monomer is composed by two polypeptide chains (HA1 and HA2) connected by a disulfide bridge. After binding to the host cell surface, IV is engulfed by endocytosis, becoming enclosed inside endosomes. The acidic pH of late endosomes triggers a large change on the structure of HA. The protein becomes extended and the first ~20 residues of the HA2 chain insert into the host membrane. This region plays a key role in the fusion process and is known as the fusion peptide (FP).
We have been working on the full-length HA and on the transmembrane peptide1, but in this talk I will present work on the HA fusion peptide and its interactions with membranes2. The fusion peptide was studied in water, DPC micelles and membrane bilayers. With these studies we found that the simulation setup has a large influence on the end result. Our studies also show that fusion peptide promotes the destabilisation of the membrane environment.