Characterising the structure and activity of the Ebola virus Delta Peptide

The Ebola virus is a highly pathogenic virus that emerged in 1976 and remains a pressing research target due to its rapid transmission and potential to cause widespread, fatal pandemics. The Ebola virus encodes seven proteins produced following infection that aid with its replication and infection of further cells. One of these proteins is a small peptide called Delta Peptide (DP) which is produced as a result of the cleavage of a glycoprotein following RNA editing. DP is one of the few Ebola proteins whose structure remains unsolved and its function is widely unknown. It is predicted that DP behaves as a Viroporin. The aim of this project was to investigate the activity of DP and how this may relate to or be dependent on its structure. DP activity was investigated through the use of dye leakage assays and a UV microscopy membrane insertion assay. These confirm predictions that DP inserts into asolectin lipid membranes and forms pores to permeabilize the membrane. DP has also been predicted to have a mainly α-helical structure using circular dichroism (CD) and nuclear magnetic resonance (NMR). The NMR experiments also demonstrate protein-lipid interactions occurring when DP was added to asolectin vesicles and suggest a structural change occurred. This project concluded that DP is likely an α-helical peptide able to inserts into asolectin membranes causing Viroporin like permeabilization. It also indicates that this membrane permeabilization is possible when DP is in its oxidised or reduced state and in the absence of its C-terminal portion and Trp25.