U of M identifies cell line that is resistant to retroviruses, including HIV

This discovery gives drug developers a target to discover new types of drugs to stop the virus from spreading.

The research, led by Nikunj Somia, Ph.D., assistant professor of Genetics, Cell Biology and Development, will be published online this week in the Proceedings of the National Academy of Sciences, and will appear in a subsequent print edition of the journal.

HIV is a parasite that does not have enough proteins of its own to complete its life cycle. To survive, the virus needs to use proteins in the cells that it infects.

Currently, the drugs that are available to fight HIV act on proteins that the virus itself produces.

“The downfall of existing HIV drugs is that since the virus is constantly changing, the drugs eventually stop working, and the virus becomes drug resistant,” Somia said. “We hypothesized that if we could find the proteins within the cells that HIV uses to make more copies of itself, we would find a potential new and more effective way to fight HIV.”

To begin their search for these proteins, they first induced mutations in cells through chemical manipulation; this made random mutations in the DNA of the cell lines. Then they altered HIV so it contained a protein that immediately kills cells, and infected the different mutant cell lines.

The Somia laboratory found that some cell lines lived after being infected with HIV. In the cell lines that live, the HIV is able to get into the cell, but it is attacked. The cell's proteasome, a “machine” in the cell that destroys or chews up proteins, attacks the virus, preventing it from making more copies of itself.

Proteasomes are signal dependant machines in the cell, and proteins are typically “tagged” to be destroyed.

“Finding the switch that turns on the proteasome machine in cells to seek and destroy the virus could be a powerful therapeutic agent in the fight against HIV and in controlling AIDS,” Somia said.