PITTSBURGH -- Carnegie Mellon University scientists have made an important discovery that aids the understanding of why HIV enters immune cells with ease. The researchers found that after HIV docks onto a host cell, it dramatically lowers the energy required for a cell membrane to bend, making it easier for the virus to infect immune cells. The finding, in press in Biophysical Journal, will provide vital data to conduct future computer simulations of HIV dynamics to help further drug discovery and prevent deadly infections.
We found that HIV fusion peptide dramatically decreases the amount of energy needed to bend a cell-like membrane, said Stephanie Tristram-Nagle, associate research professor of biological physics at Carnegie Mellon. This helps membranes to curve, a necessary step for HIV to fuse with an immune cell as it infects it.
The Carnegie Mellon scientists used X-rays to study how HIV fusion peptide (part of a larger protein) affected the energy of manufactured lipid bilayers made to mimic normal cell membranes. Lipid bilayers provide a protective barrier for the cell against intruders, yet also contain molecules to recognize and communicate with other cells or get nutrients. Cells also communicate with one another via small, membrane-bound vesicles that contain proteins or other molecular cargo. When delivering their goods, vesicles from one cell fuse with the outermost membrane of another cell to form a series of hybrid structures called fusion intermediates.
Through evolution, viruses have also become skilled at fusing with cells to unload their genetic contents, which turn host cells into virus-producing factories. In the case of HIV, a molecule called gp120 initially helps the virus lock onto its host T cell, a cell critical for maintaining immunity. Another protein gp41 then enables HIV to penetrate a T-cell membrane. Fusion takes place specifically through a short stretch of gp41 called fusion peptide 23, or FP-23 for short
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Contact: Lauren Ward
wardle@andrew.cmu.edu
412-268-7761
Carnegie Mellon University
25-Jul-2007