New technique makes cells resistant to HIV

Los Angeles: Scientists have found a way to create an HIV-resistant cell population that can quickly replace infected cells, a breakthrough that may potentially help cure the disease.

Scientists at The Scripps Research Institute (TSRI) in the US tethered HIV-fighting antibodies to immune cells, creating a cell population resistant to the virus. "This protection would be long term," said Jia Xie from The Scripps Research Institute (TSRI) in the US. The technique offers a significant advantage over therapies where antibodies float freely in the bloodstream at a relatively low concentration.

Instead, antibodies in the new technique hang on to a cell's surface, blocking HIV from accessing a crucial cell receptor and spreading infection. Xie called it the "neighbour effect." An antibody stuck nearby is more effective than having many antibodies floating
throughout the bloodstream. "You do not need to have so many molecules on one cell to be effective," he said.

Before testing their system against HIV, the scientists used rhinovirus (responsible for many cases of the common cold) as a model. They used a vector called lentivirus to
deliver a new gene to cultured human cells. This gene instructed cells to synthesise antibodies that bind with the human cell receptor (ICAM-1) that rhinovirus needs. With the antibodies monopolising that site, the virus cannot enter the cell to spread infection.

"This is really a form of cellular vaccination," said Richard Lerner, Professor of Immunochemistry at TSRI. Since the delivery system cannot reach exactly 100 per
cent of cells, the finished product was a mix of engineered and unengineered cells.
The researchers then added rhinovirus to these cell populations and waited to see what would happen. The vast majority of cells died in about two days. In dishes with only unengineered cells, the population never recovered.

There was an initial die-off in the mixed engineered/unengineered populations, too, but their numbers quickly bounced back. After 125 hours, these cell populations were back up to around the same levels as cells in an undiseased control group. In essence, the researchers had forced the cells to compete in Darwinian, "survival-of-the-fittest" selection in a lab dish. Cells without antibody protection died off, leaving protected cells to survive and multiply, passing on the protective gene to new cells.

This success led the researchers to test the same technique against HIV. To infect a person, all strains of HIV need to bind with a cell surface receptor called CD4. The scientists tested antibodies that could potentially protect this receptor on the very immune cells normally killed by HIV.

After introducing cells to the virus, the researchers ended up with an HIV-resistant population. The antibodies recognised the CD4 binding site, blocking HIV from getting to the receptor. The study was published in the journal Proceedings of the National Academy of Sciences.