UBC Reports | Vol. 47 | No. 20 | December 13, 2001

Enzyme yields clue for aids treatments

Research team uncovers trigger that impedes work of body's natural immune defense system

UBC researchers have discovered an enzyme that increases the rate of human immunodeficiency virus (HIV) infection of cells -- a finding that may lead to new AIDS therapies.

Faculty of Dentistry Prof. Christopher Overall and an interdisciplinary research team discovered that the enzyme gelatinase cuts in two the protein called Stromal Cell-Derived Factor (SDF) that normally works to slow the AIDS virus by binding to cells.

"SDF is like a traffic signal. It has many roles in the body such as directing certain white blood cells such as stem cells to stay in bone marrow," says Overall.

The HIV virus stimulates cells to produce gelatinase in excessive amounts, a process that Overall describes as "making an end-run around one of the body's natural roadblocks to infection."

"We're now trying to determine if drugs that block gelatinase can be used to boost treatments such as protease inhibitor cocktails to slow the progression of AIDS," he says.

In the mid-1990's, scientists discovered that the cell receptor that the AIDS virus uses to adhere to cells was a protein. This is a good example of how viruses can hijack normal body proteins to cause disease, says Overall.

Several anti-gelatinase drugs that tested relatively unsuccessfully as a cancer therapy may now have potential in treating AIDS, he adds.

Overall, a Canada Research Chair in Metalloproteinase Biology, says that considerable further work is needed to determine if such drugs can be effective and safe in treating AIDS patients.

"The exciting part of this discovery is that now we know that the body can be triggered to remove normal protective effects of SDF under certain circumstances," says Overall. "Now we can target these triggers as a possible avenue of treatment."

The discovery was reported last month in the Journal of Biological Chemistry. It builds on the work of research team member UBC Biochemistry Prof. Ian Clark-Lewis who reported in 1996 that synthetic variants of SDF lost their HIV-blocking ability.

Other team members include Prof. Chris Power of the University of Calgary and UBC alumnus Angus McQuibban who was part of a similar research project Overall led last year.

It found that gelatinase cut a similar protein called MCP-3 to help block inflammation such as arthritis. The widely publicized work led to several patents.