FP-23 likely plays several roles in viral fusion, according to the researchers. One role already suspected is that FP-23 attaches to its T cell victim to facilitate a change in the shape of gp41, which in turn drives uptake of HIV RNA and proteins by the T cell. But the Carnegie Mellon work suggests that FP-23 plays another, equally important function reducing the free energy of curved fusion intermediates. These fleeting shapes arise and disappear as HIV enters a T cell.
Normally, a cell membrane resists bending. Scientists can quantify the energy needed to overcome this resistance. The Carnegie Mellon team found that FP-23 reduces the energy required to penetrate an artificial cell membrane by up to 13 fold, depending on the thickness of that membrane.
Reducing this energy should help explain in part how HIV infection occurs so readily, said Tristram-Nagle. Our findings definitely will change how theoreticians think about virus-cell interactions. This same phenomenon could provide a general way that viruses use to infect cells, so it will be exciting to look at other viral systems with our experimental method, she said.
Many different viruses could enter cells by efficiently lowering the energy required to penetrate a cells outer membrane, according to Tristram-Nagle and her collaborator, John Nagle, professor of physics and biological sciences at Carnegie Mellon.
The Carnegie Mellon scientists used X-rays to detect the effect of FP-23 on lipid bilayers that mimic cell membranes. Lipid bilayers form different phases that change with temperature, but the fluid phase is the most biologically relevant. Using X-ray diffuse scattering, the team quantified structural properties of different lipid bilayers seeded with FP-23 peptides. The lipid bilayers varied in their thicknesses, which affects
Contact: Lauren Ward
Carnegie Mellon University