Chemists in the US studying how viruses enter cells say their results could help in the search for new antiviral medicines.

Viral peptide PEP1 lies flat on a vesicle surface before rearranging to form a pore across the membrane

Stanford University chemists Richard Zare and Soonwoo Chah used cell and virus models to investigate an early stage in viral infection. Using lipid spheres called vesicles as cell mimics they studied the way the vesicles rupture after exposure to PEP1, a helix-shaped peptide that resembles a peptide found in the hepatitis C virus. Zare says that 'it is important to understand how viruses interact with and break up the cell membrane. Knowledge of the exact sequence and duration of these steps is crucial to developing possible strategies for combating disease.'

When a virus invades a cell in the body, it fuses with the cell membrane and releases its genetic material into the host cell, turning into a 'chemical factory' that produces more copies of the virus. It is known that there is an intermediate stage between the time a virus merges with the cell membrane and the time it delivers its genetic contents into the cell. 'During this period, the host cell's fate hangs in the balance,' Zare explains. Cell infection is often irreversible once a virus has penetrated the cell - so this stage 'may represent an opportunity for drug development,' suggests Zare. 

Zare and Chah investigated the intermediate stage more closely using surface plasmon resonance (SPR) microscopy to measure the lipids' optical properties. Since these properties are different for intact and ruptured vesicles, SPR allows the researchers to follow the rupture mechanism in real time. The researchers found that, after introducing the peptide to the vesicles, the peptides first lie flat on the surface then switch to cross the membrane, forming pores. 'This attack causes the vesicles to transform into a lipid bilayer,' says Zare. 

Richard Epand, a biochemist from McMaster University, Hamilton, Canada, is impressed. He says that although using a viral peptide and not the intact virus means there are some limitations, the work 'could contribute significantly to our understanding of viral fusion processes.' 

Michael Spencelayh