AIDS virus accepts toxic Trojan horse.

AIDS virus accepts toxic Trojan horse

Researchers have harnessed a cancerfighting toxin to a genetically engineered protein and produced a potentially potent new weapon against AIDS.

The AIDS virus, or human immunodeficiency virus (HIV), can infect an immune cell when it locks onto a cell receptor protein called CD4. After using this as an avenue to enter the cell, HIV can make many copies of itself, and some HIV proteins end up on the outside of the cell. If a highly toxic molecule is attached to genetically engineered CD4 proteins, laboratory tests show the HIV protein on infected cells will attach to those CD4 proteins and the toxin will enter and kill the cell, report scientists from the University of Texas Southwestern Medical Center at Dallas and Genentech, Inc. in South San Francisco, in the Nov. 25 SCIENCE.

The technique uses the virus' own infectious mechanisms against it, explains one of the researchers. "The virus thinks it's seeing another cell with CD4, and unfortunately for it, it's seeing a CD4 with a toxin attached," says Ellen S. Vitetta of the Southwestern Medical Center.

The toxin, ricin, has already been tested in 1,000 cancer patients using a similar technique, Vitetta says. To kill cancer cells, researchers attach the toxin to monocolonal antibodies that only latch onto cancer cells.

In the laboratory, the CD4-ricin combination attacks HIV-infected cells 1,000 times more often than non-infected cells, the researchers say. There are some cells that naturally interact with other cell's CD4 proteins, and there was some worry that these cells might also take up the toxin-CD4 combination. The toxic duo probably won't be a cure for AIDS because some infected cells don't have copies of HIV proteins on the cell exterior, but it might be possible to kill enough infected cells to prevent the disease from spreading and causing the life-threatening AIDS symptoms, they add.

"What we want to do is create a standoff" between HIV and the toxin, Vitetta says. "If you could create a standoff for thirty years or so you have effectively won the game," she adds.

If further research goes well, a CD4-ricin compound could be ready for clinical testing in a year or so, but there are still a lot of questions that have to be answered, Vitetta says. One important issue is whether the cells killed by the toxin release active AIDS viruss that could go out and infect other cells. Researchers also need to know if the CD4-ricin combination will work against the many other strains of HIV and all the different types of immune cells that can be infected by HIV, she adds.