St. Louis, Jan. 5, 1999 -- Like a man strapped to a pack of dynamite, HIV-infected cells will self-destruct when rigged with a lethal protein combination. The virus lights the fuse when it tries to reproduce.

The study, reported today in the January issue of Nature Medicine, makes use of a new technology for introducing large proteins into cells -- a long-held dream of the pharmaceutical industry.

"This Trojan horse approach should be applicable to many other infectious diseases, such as hepatitis C, malaria and herpes," says Steven F. Dowdy, Ph.D., who led the research. "We also hope that future modifications will allow us to selectively kill cancer cells."

Dowdy is an assistant investigator of the Howard Hughes Medical Institute and an assistant professor of pathology and medicine at Washington University School of Medicine in St. Louis. Adita M. Vocero-Akbani, Ph.D., a research associate of the Howard Hughes Medical Institute, is the paper's lead author. The work was performed in collaboration with Nancy Vander Heyden, a research associate in the laboratory of Lee Ratner, M.D., Ph.D., professor of medicine, molecular microbiology and pathology.

"This novel method of introducing cytotoxic proteins into HIV-1-infected cells is a therapeutic approach that could complement antiviral drugs that are currently in clinical use," Ratner says.

The virus that causes AIDS uses a scissors-like protein called a protease to cut out enzymes it needs for reproduction. Drugs called protease inhibitors, which are extending many lives, sit in the hinge of the scissors, preventing them from doing their job. But mutations in the protease can make the drugs ineffective. The drugs also inhibit a patient's own proteases, so they often are toxic.

Riding his bike to work one day, Dowdy thought, "Why not use the viral protease to kill the cell instead of using a drug to inactivate the protease?"
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Contact: Linda Sage
sage@medicine.wustl.edu
314-286-0119
Washington University School of Medicine
4-Jan-1999