Amyloid fibrils are form of highly ordered, β-sheet protein structure found in many sites in the body. Fibrils are associated with many diseases, particularly neurological ones, eg Alzheimer’s and Parkinson’s. Fibril formation occurs when intermediates along the protein-folding pathway irreversibly inter the off folding pathway to form highly ordered amyloid fibrils as shown in figure 1. This process is not limited to disease-related proteins and normal proteins can form amyloid fibrils under appropriate conditions (Carver et al. 2003). Protein fibrils enhance HIV infection. Semen contains a fibril forming component that significantly increases the ability of HIV to infect cells. This peptide is associated with peptide fragments of prostatic acid phosphatase and has been termed semen-derived enhancer of virus infection (SEVI). SEVI acts as the virus entry stage and only boosts infectivity when the peptide has folded into highly structured arrays of amyloid fibrils (Münch et al. 2007).

The proposal is to investigate whether SEVI is toxic to cells and whether amyloid fibrils have broader roles in HIV infection than just at the transmission stage. The project also accesses the ability of anti-fibril agent, clusterin, to reduce infection in vitro. Preliminary results imply that SEVI is toxic to pheochromocytoma cells (PC12) at very low concentration. SEVI also have amyloidogenic regions that form fibrils that are toxic to PC 12 cells as well. Future modelling will attempt to show how SEVI interact with the HIV envelop protein, GP 120 and whether clusterin can prevent cytotoxicity associated with SEVI.