Genetically engineered T cells render HIV's harpoon powerless

When HIV attacks a T cell, it attaches itself to the cell's surface and launches a "harpoon" to create an opening to enter and infect the cells. 

To stop the invasion, researchers from the Penn Center for AIDS Research at the University of Pennsylvania and scientists from Sangamo BioSciences, Inc. have developed genetically engineered T cells armed with a so-called "fusion inhibitor" to disrupt this critical step and prevent a wide range of HIV viruses from entering and infecting the T cells. The findings were reported today online in a preclinical study in PLOS Pathogens.

HIV medicine experienced a breakthrough in the early 2000s with a unique class of drugs known as "fusion inhibitors." Unlike most drugs that block virus replication inside of T cells, these drugs prevent HIV from entering cells in the first place. The drug, enfuvirtide, modeled after a peptide from the viral envelope and used today in combination with other antiretroviral therapies, has been shown to keep the virus at bay. However, patients need to inject enfuvirtide daily under their skin. HIV can also become resistant to enfuvirtide.

Building on this approach with a powerful genetic technique, researchers developed a novel way to deliver the fusion inhibitor peptide precisely to the spot on the cell surface where the virus attaches and launches its envelope, like a harpoon. The team genetically altered T cells by introducing a so-called C34 peptide, modeled after enfuvirtide, directly onto receptors, CXCR4 and CCR5, which are crucial for HIV entry.

By using these molecules to deliver the C34 peptide to the site where the virus enters, these investigators showed that HIV was potently inhibited and that this inhibition extended to genetically diverse HIVs, including those that were resistant to the drug, enfuvirtide.